Disaccharides for drug discovery

ABSTRACT

Methods are described for the preparation of combinatorial libraries of potentially biologically active disaccharide compounds. These compounds are variously functionalized, with a view to varying lipid solubility size, function an other properties, with the particular aim of discovering novel drug or drug-like compounds, or compounds with useful properties. The invention provides intermediates, processes and synthetic strategies for the solution or solid phase synthesis of disaccharides, variously functionalized about the sugar ring, including the addition of aromaticity and charge, and the placement of pharmaceutically useful groups and isosteres.

FIELD OF THE INVENTION

This invention relates to methods for the preparation of combinatoriallibraries of potentially biologically active disaccharide compounds.These compounds are variously functionalized, with a view to varyinglipid solubility, size, function and other properties, with theparticular aim of discovering novel drug or drug-like compounds, orcompounds with useful properties. The invention provides intermediates,processes and synthetic strategies for the solution or solid phasesynthesis of disaccharides, variously functionalised about the sugarring, including the addition of aromaticity and charge, and theplacement of pharmaceutically useful groups and isosteres.

BACKGROUND OF THE INVENTION

From a drug discovery perspective, carbohydrate pyranose and furanoserings and their derivatives are well suited as templates. Each sugarrepresents a three-dimensional scaffold to which a variety ofsubstituents can be attached, usually via a scaffold hydroxyl group,although occasionally a scaffold carboxyl or amino group may be presentfor substitution. By varying the substituents, their relative positionon the sugar scaffold, and the type of sugar to which the substituentsare coupled, numerous highly diverse structures are obtainable. Animportant feature to note with carbohydrates, is that moleculardiversity is achieved not only in the type of substituents, but also inthe three dimensional presentation. The different stereoisomers ofsaccharides that occur naturally (examples include glucose, galactose,mannose etc), offer the inherent structural advantage of providingalternative presentation of substituents.

Although there are a number of examples of monosaccharides being used asscaffolds for drug discovery purposes^(i,ii,iii), there are only alimited number of examples of disaccharides or higher saccharides beingused as templates for the presentation of pharmaceutically usefulfunctional groups.

Derivatised disaccharides and higher saccharides, represent a new classof compounds for drug discovery that are able to address a significantand different group of receptors from those addressed by monosaccharidescaffolds. This group or receptors can be broadly described as thosereceptors in which the critical binding groups are distal to each other.In principle, monosaccharide scaffolds can be used to address up to fivebinding groups (more usually 3 binding groups would be chosen), theconnection points on the scaffold are each separated by between 1 and 5angstroms in space. Disaccharide scaffolds on the other hand canaccommodate up to eight binding groups although more usually 3-4 bindinggroups would be chosen, the connection points for each of these groupsbeing separated by as much as 10 angstroms in space. Obviously theappended functional groups may be separated by even greater distances in3-dimensional space. The replacement of the glycosidic bond linking thetwo monosaccharide components with a spacer group can further increasethe separation between binding groups of interest.

The ability to address more distally placed binding groups is animportant feature for a number of biological receptor moleculesincluding the G-protein coupled receptors, where at the extra-cellularopening to many of these receptors, the width of the binding channel isup to 14 angstroms. Additionally, disaccharide scaffolds can be used asprobes of interactions which involve large surface areas for example theprotein-protein interaction of the CD4-GP120 system, an importantinteraction in the aetiology of the human immunodeficiency virus.

Through the development of a range of selectively protected and modifiedmonosaccharide, cyclitols and tetrahydropyran building blocks, we havedeveloped a system that allows the chemical synthesis of highlystructurally and functionally diverse derivatised disaccharide anddisaccharide analogue structures, of both natural and unnatural origin.The diversity accessible is particularly augmented by the juxtapositionof both structural and functional aspects of the molecules. In order toaccess a wide range of diverse structures, stereo-center inversionchemistry is required, so as to achieve non-naturally occurring and hardto get sugars and sugar analogues in a facile manner. Other chemistriesare also required that provide unnatural deoxy or deoxy amino derivativewhich impart greater structural stability to the drug-like targetmolecules. With a suite of reagents to effect a suitable range ofchemistries on a solid support, allowing such things as; wide functionaldiversity, highly conserved intermediates, a limited number of commonbuilding block to be required, and with suitable chemistry to allowaccess to unusual carbohydrate stereo-representations and includingaccess to deoxy and deoxy amino analogues, a methodology is thenestablished that can create focused libraries for a known target, oralternatively diversity libraries for unknown targets for randomscreening.

It will be clearly understood that, although a number of prior artpublications are referred to herein, this reference does not constitutean admission that any of these documents forms part of the commongeneral knowledge in the art, in Australia or in any other country.

Many of the traditional methods of carbohydrate synthesis have proved tobe unsuitable to a combinatorial approach, particularly because modernhigh-throughput synthetic systems require procedures to be readilyautomatable. The compounds and processes described herein areparticularly suited to the solid and solution phase combinatorialsynthesis of carbohydrate-based libraries, and are amenable toautomation. The methods of the invention yield common intermediates thatare suitably functionalized to provide diversity in the structure of thecompounds so generated. Using the method described, it is possible tointroduce varied functionality in order to modulate both the biologicalactivity and pharmacological properties of the compounds generated.

Thus the compounds and methods disclosed herein provide the ability toproduce random or focused combinatorial-type libraries for the discoveryof other novel drug or drug-like compounds, or compounds with otheruseful properties in an industrially practical manner.

SUMMARY OF THE INVENTION

In a first aspect, the invention provides disaccharide compounds offormula I

A-d-L-e-B  formula I

In which the groups A and B are independently chosen from

in which the ring may be of any configuration and the anomeric centerwhere present may be of either the α or β configuration;

Independently for each ring

T may be O or CH₂;

R6 and R7 are hydrogen, or together form a carbonyl oxygen;

R1 may be hydrogen, —N(Z)Y, C(Z)Y, OZ or SZ wherein;

When R1 is N(Z)Y

Y is selected from hydrogen, or the following;

Z is selected from hydrogen or X1;

Q is selected from hydrogen or W;

The groups Z and Y may be combined to form a monocyclic or bicyclic ringstructure of 4 to 10 atoms. This ring structure may be furthersubstituted with X1 groups;

The groups W are independently selected from alkyl, alkenyl, alkynyl,heteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20atoms which is optionally substituted, branched and/or linear. Typicalsubstituents include but are not limited to OH, NO, NO₂, NH₂, N₃,halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy, aryloxy, amidine,guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acidamide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl,aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted orunsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide,hydrazide, hydroxamate, hydroxamic acid;

The groups X1 are independently selected from alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkylor heteroarylalkyl of 1 to 20 atoms which is optionally substituted,branched and/or linear. Typical substituents include but are not limitedto OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy,aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acid ester,carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl,aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl,substituted or unsubstituted imine, sulfate, sulfonamide, phosphate,phosphoramide, hydrazide, hydroxamate, hydroxamic acid;

Where R1 is C(Z)Y;

Y, where present, is selected from hydrogen, double bond oxygen (═O) toform a carbonyl, or triple bond nitrogen to form a nitrile.

Z may be optionally absent, or is selected from hydrogen or X2

Wherein X2 is independently selected from alkyl, alkenyl, alkynyl,heteroalkyl, aminoalkyl, aminoaryl, aryloxy, alkoxy, heteroaryloxy,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, acyl,arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyl or heteroarylalkylof 1 to 20 atoms which is optionally substituted, branched and/orlinear. Typical substituents include but are not limited to OH, NO, NO₂,NH₂, N₃, halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy, aryloxy, amidine,guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acidamide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl,aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted orunsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide,hydrazide, hydroxamate, hydroxamic acid, heteroaryloxy, aminoalkyl,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, whichmay optionally be further substituted;

The groups Z and Y may be combined to form a monocyclic or bicyclic ringstructure of 4 to 10 atoms. This ring structure may be furthersubstituted with X1 groups;

Where R1 is OZ or SZ,

Z is selected from hydrogen or X3,

Wherein X3 is independently selected from alkyl, alkenyl, alkynyl,heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkylor heteroaryialkyl of 1 to 20 atoms which is optionally substituted,branched and/or linear. Typical substituents include but are not limitedto OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy,aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acid ester,carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl,aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl,substituted or unsubstituted imine, sulfate, sulfonamide, phosphate,phosphoramide, hydrazide, hydroxamate, hydroxamic acid, heteroaryloxy,aminoalkyl, aminoaryl, aminoheteroaryl, thioalkyl, thioaryl orthioheteroaryl, which may optionally be further substituted;

The groups R2, R3, R4 and R5 are independently selected from the groupconsisting of hydrogen, N₃, OH, OX4, N(Z)Y, wherein N(Z)Y is as definedabove or additionally Y is

where Q and W are as defined above, and X4 is independently selectedfrom alkyl, alkenyl, alkynyl, heteroalkyl, aminoalkyl, aminoaryl,aryloxy, alkoxy, heteroaryloxy, aminoaryl, aminoheteroaryl, thioalkyl,thioaryl or thioheteroaryl, acyl, arylacyl, heteroarylacyl, aryl,heteroaryl, aryalkyl or heteroarylalkyl of 1 to 20 atoms which isoptionally substituted, branched and/or linear. Typical substituentsinclude but are not limited to OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂,CH₂F, nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid,carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl,heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl,aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate,sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate,hydroxamic acid;

The groups Z and Y may be combined to form a monocyclic or bicyclic ringstructure of 4 to 10 atoms. This ring structure may be furthersubstituted with X1 groups;

The groups A and B are linked together with a linking structure d-L-e,in which the groups d and e represent the connection points for A and Band replace one of the groups R1, R2, R3, R4, or R5 in each of thegroups A and B and form the connection point for the linker L.The groups d and e are independently chosen from a covalent bond or thefollowing list:

L may be absent, or is selected from alkyl, cycloalkyl, alkenyl,cycloalkenyl, alkynyl, heteroalkyl, cycloheteroalkyl, aryl, heteroaryl,arylalkyl or heteroarylalkyl of 1 to 12 atoms which is optionallysubstituted, branched and/or linear, saturated or unsaturated. Typicalsubstituents include but are not limited to OH, NO, NO₂, NH₂, N₃,halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy, aryloxy, amidine,guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acidamide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl,aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted orunsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide,hydrazide, hydroxamate, hydroxamic acid, heteroaryloxy, aminoalkyl,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, whichmay optionally be further substituted;

It is understood that the rules of molecular stoichiometry will beupheld by the default addition of hydrogens atoms as required.

A preferred embodiment of the first aspect provides for compounds offormula I in which

-   -   in group A, T is oxygen,    -   group A is a pyranose ring,    -   The linker, d-L-e, is a glycosidic linkage formed between the        anomeric position R1 of group A, and any position R1 to R5 of        group B, such that the d is (—O—), L is absent, and e is a        covalent bond.

-   Importantly, The R groups on each ring may be selected independently    from each other. For example, R2 on ring A may be different from R2    on ring B.    Exemplary structure of this embodiment include but are not limited    to:

Another preferred embodiment of the first aspect provides for compoundsof formula I in which

-   -   In group A, T is oxygen,    -   group A is a pyranose ring,    -   The linker, d-L-e, forms an amide linkage in which R6 and R7 of        A is a C═O, R5 is d which is a covalent bond, L is absent, and        any of R1, R2, R3, R4, R5 on B is e which is

-   Importantly, The R groups on each ring may be selected independently    from each other. For example, R2 on ring A may be different from R2    on ring B.    Exemplary structure of this embodiment include but are not limited    to:

Another preferred embodiment of the first aspect provides for compoundsof formula I in which

-   -   in group A, T is oxygen,    -   both groups A and B are pyranose rings,    -   The linkage, d-L-e, is an ether type linkage in which any of R1        to R5 in group A and group B is d and e respectively and is

-   -   and L must be present.

-   Importantly, The R groups on each ring may be selected independently    from each other. For example, R2 on ring A may be different from R2    on ring B.    Exemplary structure of this embodiment include but are not limited    to:

Another preferred embodiment of the first aspect provides for compoundsof formula I in which

In group A, T is oxygen,

-   -   The linkage, d-L-e, is a linkage in which R1 in group A is d,        which is chosen from: a covalent bond;

L must be present;

and e is

-   Importantly, The R groups on each ring may be selected independently    from each other. For example, R2 on ring A may be different from R2    on ring B.    Exemplary structure of this embodiment include but are not limited    to:

Another preferred embodiment of the first aspect provides for compoundsof formula I in which

In group A, T is oxygen,

-   -   The linkage, d-L-e, is a linkage in which R1 in group A is d, R1        in group B is e, and both d and e are independently chosen from:        a covalent bond;

L must be present;

-   Importantly, The R groups on each ring may be selected independently    from each other. For example, R2 on ring A may be different from R2    on ring B.    Exemplary structures of this embodiment include but are not limited    to:

Another preferred embodiment of the first aspect provides for compoundsof formula I in which

In group A, T is oxygen,

The linker, d-L-e, is a linkage in which any R group R1 to R5 in group Amay be d and is selected from

And any R group R1 to R5 in group B may be e and e is

L must be present.

-   Importantly, The R groups on each ring may be selected independently    from each other. For example, R2 on ring A may be different from R2    on ring B.-   Exemplary structures of this embodiment include but are not limited    to the list below.

Another preferred embodiment of the first aspect provides for compoundsof formula I in which

In group A, T is oxygen,

The linkage, d-L-e, is a linkage in which any R group R1 to R5 in groupsA and B may be d and e respectively and d and e are independentlyselected from

L must be present.

-   Importantly, The R groups on each ring may be selected independently    from each other. For example, R2 on ring A may be different from R2    on ring B.-   Exemplary structures of this embodiment include but are not limited    to the list below.

In a second aspect, the invention provides for a method of synthesis ofcompounds of formula I comprising the step of reacting two appropriatelysubstituted and protected monosaccharide compounds A and B in solution,In a third aspect, the invention provides for a method of combinatorialsynthesis of compounds of the formula I comprising the step ofimmobilizing a compound of group B onto a support through any of thefunctionalized positions R1 to R5. Said support may be soluble orinsoluble. Non-limiting examples of insoluble supports includederivatised polystyrene, tentagel, wang resin, MBHA resin,aminomethylpolystyrene, rink amide resin etc. Non-limiting examples ofsoluble supports include DOX-mpeg, polyethylene glycol etc.Compounds of the invention are useful in screening for biologicalactivity.

For the purposes of this specification it will be clearly understoodthat the word “comprising” means “including but not limited to”, andthat the word “comprises” has a corresponding meaning.

General Method 1: Urea Formation

To the diamine (1.05 mmol) dissolved in N,N-dimethylformamide (11 mL),was added isocyanate (1.99 mmol), and the solution stirred for 2.5 h.Toluene (20 mL) was added and all solvent removed to leave an oil. Thisprocedure was repeated twice more. This residue was then triturated withether and the resulting solid filtered to afford the product.

General Method 2: Transesterification

To a solution of the sugar (16.2 mmol) in a 1:1 mixture ofmethanol/dichloromethane (110 mL) was added sodium methoxide (6.5 mmol)and the whole stirred under nitrogen for 2 h. Amberlite IR 120 H⁺ wasadded until pH 5 was reached. The resin was filtered off and washedseveral times with methanol and the combined filtrates were thenconcentrated to dryness to leave a residue. The residue was eithertriturated with ether or purified by column chromatography to give thedesired product.

General Method 3: Azide Reduction

To a solution of the azido compound (0.30 mmol) in 4:1N,N,-dimethylformamide/methanol (5 mL) was added a solution of ammoniumchloride (1.50 mmol) in water (0.5 mL). Activated zinc dust (8.98 mmol)was then added and the suspension stirred for 40 min. A second additionof ammonium chloride (0.50 mmol) in water (0.25 mL) and zinc dust (1.5mmol) was made and the suspension stirred for a further 40 min. Afterthis time chloroform (50 mL) was added and the suspension filteredthrough celite and washed with chloroform/N,N,-dimethylformamide (1:1).These combined filtrates were then washed with brine, dried (MgSO₄), andall solvent removed in vacuo to typically leave solid.

General Method 4: HBTU Coupling

To a solution of the acid (0.05 mmol) and HBTU (0.05 mmol) in dryN,N,-dimethylformamide (0.2 mL) was added diisoproplyethylamine (0.03mL, 0.17 mmol) and the whole stirred for 10 min. A solution of the sugaramine (0.04 mmol) in dry N,N,-dimethylformamide (0.3 mL) was then addedand the whole stirred for 16 h. Chloroform (15 mL) was then added andwashed with water, 10% citric acid, saturated sodium hydrogen carbonate,brine, dried (MgSO₄), and the solvents removed in vacuo to leave an oil.The crude was typically carried through to the next step without furtherpurification.

General Method 5: Global Deprotection for Formation of the FinalProduct-1.

The sugar (0.04 mmol) was dissolved in a solution (3 mL) of 93% drydichloromethane, 5% triethylsilane, 2% trifluoroacetic acid and thereaction stirred at room temperature for 2 hours. The solvents were thenremoved in vacuo and the solution then freeze-dried to leave a whitesolid. This solid was then purified by prep HPLC.

General Method 6: Global Deprotection for Formation of the FinalProduct-2.

The sugar (0.0016 mmol) was dissolved in a solution (0.1 mL) of 83% drydichloromethane, 15% p-thiocresol, 2% trifluoroacetic acid and thereaction stirred at room temperature for 0.5 hours. The solvents werethen removed in vacuo to give the crude product.

General Method 7: DIC Coupling

To the acid (52 μmol) and HOBT (52 μmol) in dry DCM (1 mL) and dry DMF(1 drop) was added DIC (52 μmol). The solution was stirred for 1 minthen added to a solution of amine (35 μmol) in dry DCM (1 mL). Thereaction mixture was stirred at room temperature for 1 h then dilutedwith DCM, washed with 10% citric acid, saturated hydrogen carbonate,brine, dried over MgSO₄ and the solvents removed in vacuo.

General Method 8: Ester Hydrolysis

To crude product 4 in dioxane (0.6 mL) was added 1M aq. KOH (0.6 mL).The reaction mixture was stirred at room temperature for 1 h thenconcentrated in vacuo. The residue was dissolved in CH₃CN (2 mL) and DCM(0.5 mL) and stirred with Amberlite for 1 h. The solution was filteredand concentrated in vacuo to yield a residue which was subsequentlypurified by prep HPLC.

General Method 9: Fmoc Cleavage Followed by DIC Coupling

Fmoc protected amino compound (˜50 μmol) was dissolved in acetonitrile(2.4 mL) and piperidine (60 μL, 0.60 μmol) was added. The mixture wasstirred over night, the solvents evaporated in vacuo and the residueazeotroped with toluene to afford a residue. The residue was taken up indry dichloromethane (2 mL) and a solution of octanoic acid (12 μL, 75μmol) and DIC (12 μL, 75 μmol) in dry dichloromethane (2 mL) (stirredfor 5 min at room temperature prior to addition) was added. Stirring wascontinued for 1 h and the mixture was diluted with dichloromethane (50mL), washed with 10% citric acid, satd. sodium bicarbonate solution,filtered over a pad of cotton, and the solvents removed in vacuo toafford the product as a crude mixture.

General Method 10: Amine Deprotection

The fully protected block [2 mmol] was suspended in butanol (15 ml) andethylene diamine (15 ml) and the mixture heated at reflux for 20 h. Thesolvents were evaporated, the residue taken up in chloroform, washedwith dilute brine, dried (MgSO₄) and evaporated. The compound was loadedonto a pad of silica with chloroform and eluted with 9% methanol inchloroform to yield the pure diamine quantitatively.

General Method 11: Diamine Coupling

The diamine (17 mg, 0.023 mmol) was dissolved in dry chloroform (0.5ml), DIPEA (3 mg, 4 μl, 1 equiv) added and the solution cooled to −78°C. A solution of FMOC-Cl (4.2 mg, 0.7 equiv) in chloroform (0.2 ml) wasadded dropwise and allowed to warm to it slowly before stirring for 16h. The mixture was partitioned between chloroform and water, the organiclayer washed with NaHCO₃, brine, dried (MgSO₄) and evaporated todryness. This gave the monoprotected amine as the major product.

General Method 12: Thiourea Formation

To a solution of the sugar (0.48 mmol) in N,N-dimethylformamide (4.8mL), was added 4-fluorophenylisothiocyanate (0.48 mmol), and thesolution stirred at room temperature for 4 h. Toluene (5 mL) was addedand all solvent removed to leave an oil.

General Method 13: CBz Formation

To a solution of the sugar (0.48 mmol) in chloroform (4.8 mL), was addeddiisopropylethylamine (0.52 mmol). After 5 minutes benzyl chloroformate(0.52 mmol) was added and the solution stirred at room temperature for 2h. Chloroform (5 mL) was then added and washed with water, 10% citricacid, saturated sodium hydrogen carbonate, brine, dried (MgSO₄), and thesolvents removed in vacuo to leave an oil.

General Method 14: Sulphonamide Formation

To a solution of the sugar amine (0.0267 mmol) and diisopropyethylamine(0.014 ml, 0.08 mmol) in dry dichloromethane (0.25 mL), was addedp-toluenesulfonyl chloride (10.2 mg, 0.054 mmol) and the solutionstirred for 72 hrs. The reaction mixture was diluted with drydichloromethane (2 mL), washed with water (2 ml), dried (MgSO₄), and thesolvents removed in vacuo to afford the product as a crude mixture.

General Method 15: Acylation with Acetic Anhydride

To a solution of the sugar amine (0.04 mmol) and diisopropyethylamine(0.02 ml, 0.12 mmol) in dry dichloromethane (0.4 mL) was added dropwiseacetic anhydride (0.015 mL, 0.12 mmol) and the solution stirred for 1 h.The solution was concentrated in vacuo to yield the crude product.

General Method 16: Fmoc Cleavage

Fmoc protected amino compound (0.48 mmol) was dissolved in chloroform (4mL) and piperidine (1 ml). The mixture was stirred for 1 hr, evaporatedto dryness. The residue was taken up in acetonitrile (4 ml) and thesolid was filtered off and the filter cake washed with acetonitrile (1ml). The acetonitrile solutions were combined and evaporated to dryness.The residue was purified by column chromatography(dichloromethane:methanol 20:1) to afford the desired product,

General Method 17: Hydrolysis of Trifluoroacetate Ester and Purificationof the Final Products,

The sugar (0.04 mmol) was dissolved in a solution of methanol (2 mL) andconcentrated aqueous ammonium hydroxide (2 ml); the reaction stirred atroom temperature for 2 hours. The solvents were then removed in vacuoand the solution then freeze-dried to leave a white solid. This solidwas then purified by prep HPLC.

EXAMPLE 1 Preparation of a Compound with a Glycosidic Linkage asDescribed by Compounds of Formula II

EXAMPLE 2 Preparation of a Compound with an Amide Linkage as Describedby Compounds of Formula III

EXAMPLE 3 Preparation of a Compound with an Ether Linkage as Describedby Compounds of Formula IV

EXAMPLE 4 Preparation of a Compound with an Ether Linkage as Describedby Compounds of Formula IV

EXAMPLE 5 Preparation of a Compound with an Ether Linkage as Describedby Compounds of Formula V

EXAMPLE 6 Preparation of a Compound with a Linkage as Described byCompounds of Formula V and VI

EXAMPLE 7 Preparation of a Compound with a Linkage as Described byCompounds of Formula VI

EXAMPLE 8 Preparation of a Compound with a Linkage as Described byCompounds of Formula VII

EXAMPLE 9 Preparation of a Compound with a Linkage as Described byCompounds of Formula VIII

EXAMPLE 10 Synthesis of 1,5-Anhydrogalactitol Acceptor

10-a. Synthesis of1,5-anhydro-4-azido-2,4-dideoxy-2-DTPM-6-O-(4-methoxybenzyl)-D-galactitol(56)

Compound 56 was prepared according to the procedure described in GeneralMethod 2, δ_(H) (400 MHz; CDCl₃) 3.25 (3H, s), 3.26 (3H, s), 3.65 (5H,m), 3.80 (3H, s), 4.09 (3H, m), 4.50 (2H, q, J 9.5 Hz and J 3.6 Hz),6.89 (2H, d, J 8.8 Hz), 7.26 (2H, d, J 8.8 Hz), 8.21 (1H, d, J 13.6 Hz),and 10.15 (1H, br t, J 11.4 Hz); LCMS [M+H]⁺ 475.

10-b. Synthesis of2-amino-1,5-anhydro-4-azido-2,4-dideoxy-6-O-(4-methoxybenzyl)-D-galactitol(57)

To a solution of the sugar 56 (16.0 mmol) in a 3:1 mixture of drymethanol/N,N,-dimethylformamide (120 mL) was added hydrazine monohydrate(86.3 mmol) and the resulting reaction mixture was stirred for 3 h. Theresulting precipitate was removed by filtration and the filtrateconcentrated in vacuo. The residue was then redissolved indichloromethane, washed with saturated sodium chloride, dried (MgSO₄)and all solvent removed under reduced pressure to leave a solid 57. Thesolid was used directly in the next step.

10-c. Synthesis of1,5-anhydro-4-azido-2-(3-carboxybenzyl)-2,4-dideoxy-6-O-(4-methoxybenzyl)-D-galactitol(58)

To a solution of the amine 57 (16.2 mmol) in methanol (55 ml), was addedphthalic anhydride (216.2 mmol), and the whole stirred for 2 h. Themixture was then evaporated to dryness under reduced pressure and theresidue azeotroped with toluene to leave a cream solid 58.

10-d. Synthesis of3-O-acetyl-1,5-anhydro-4-azido-2,4-dideoxy-6-O-(4-methoxybenzyl)-2-phthallimido-D-galactitol(59)

The acid 4 (16.3 mol) was suspended in dry pyridine (19 ml), cooled to0° C., and acetic anhydride (48.7 mmol) added. The suspension was thenstirred for 1 h at 0° C. followed by 18 h at room temperature. Thesolvent was then removed in vacuo and the resulting residue azeotropedwith toluene, redissolved in chloroform and washed with water, 10%citric acid, saturated sodium hydrogen carbonate, brine, dried (MgSO₄)and the solvent removed in vacuo to leave a yellow solid 59.

10-e. Synthesis of1,5-Anhydro-4-azido-2,4-dideoxy-6-O-(4-methoxybenzyl)-2-phthallimido-D-galactitol(60)

Compound 60 was prepared according to the procedure described in GeneralMethod 2, yield (77% from 55), δ_(H) (400 MHz; CDCl₃) 3.58 (1H, dd, J14.3 Hz and J 7.3 Hz), 3.66-3.74 (1H, m), 3.82 (3H, s), 3.82-3.93 (1H,m), 4.03 (1H, t, J 11.4 Hz), 4.10 (1H, d, J 3.7 Hz), 4.42-4.52 (1H, m),4.52 (2H, s), 4.66 (1H, dd, J 3.7 Hz and J 10.7 Hz), 6.90 (2H, d, J 8.9Hz), 7.28 (2H, d, J 8.9 Hz), 7.74 (2H, m) and 7.67 (2H, m);[M+NH₄]⁺=456.

EXAMPLE 11 Synthesis of a Trichloroacetimidate Donor

11-a. Thiomethyl2-azido-2-deoxy-3,4,6-tri-O-(4-methoxybenzyl)-β-D-glucopyranoside (62)

The thioglycoside 61 (21.2 mmol) was added in portions to a suspensionof sodium hydride (84.8 mmol) in DMF (106 ml) at 0° C. After 20 min, themixture was allowed to return to room temperature and stirred for 30 minprior to recooling to 0° C. To the suspension was then added4-methoxybenzyl chloride (11.5 ml) over 20 mins. The reaction mixturewas then allowed to return to room temperature and stirred for 16 h. Theresulting solution was cooled to 0° C. and quenched with ammoniumchloride solution. The reaction mixture was partitioned between waterand chloroform, and the organic layer subsequently washed with brine,dried (MgSO₄) and evaporated. Residue was purified by columnchromatography to give the desired product 62 as a solid in quantitativeyield, δ_(H) (400 MHz; CDCl₃) 2.22 (3H, s), 3.32-3.48 (3H, m), 3.54-3.70(3H, m), 3.80 (3H, s), 3.81 (3H, s), 3.82 (3H, s), 4.17 (1H, d, J 9.5Hz), 4.46 (1H, d, J 9.3 Hz), 4.49 (1H, d, J 10.3 Hz), 4.55 (1H, d, J11.6 Hz), 4.63 (1H, d, J 5.2 Hz), 4.82 (2H, s), 6.75-6.95 (6H, m), 7.09(2H, d, J 8.9 Hz), 7.24 (2H, d, J 8.9 Hz) and 7.30 (2H, d, J 10.3 Hz);LCMS [M+Na]⁺=618.2.

11-b. Synthesis of2-Azido-2-deoxy-3,4,6-tri-O-(4-methoxybenzyl)-D-glucopyranose (63)

To a solution of thioglycoside 62 (112.9 mmol) in acetone (450 mL) at 0°C., shielded from light, was added water (277.8 mmol), N-iodosuccinimide(134.9 mmol), followed by TMSOTf (11.2 mmol), and the solution stirredfor 90 min. Chloroform (400 mL) was added and the chloroform layerseparated and washed with saturated sodium hydrogen carbonate solution,saturated Na₂S₂O₃ solution, brine, dried (MgSO₄) and concentrated invacuo to leave a solid. The solid was triturated with ether to give thedesired product 63 as a cream coloured solid (98%), δ_(H) (400 MHz;CDCl₃) 3.42 (1H, dd, J 3.0 Hz and J 10.0 Hz), 3.52-3.66 (3H, m), 3.78(3H, s), 3.81 (3H, s), 3.82 (3H, s), 3.97 (1H, t, J 9.8 Hz), 4.03 (1H,dq, J 2 Hz, J 4.9 Hz and J 9.8 Hz), 4.42 (2H, t, J 10.3 Hz), 4.53 (1H,d, J 11.8 Hz), 4.62 (1H, br d, J 4.9 Hz), 4.73 (1H, d, J 10.6 Hz), 4.82(2H, s), 6.81-6.93 (6H, m), 7.05 (2H, d, J 8.8 Hz), 7.24 (2H, d, J 11.7Hz) and 7.30 (2H, d, J 8.8 Hz); LCMS [M+Na]⁺=588.3.

11-c. Synthesis of2-Amino-2-deoxy-3,4,6-tri-O-(4-methoxybenzyl)-D-glucopyranose (64)

To a solution of the azide 63 (110.2 mmol) in dry DMF (275 mL) was addeddithiothreitol (220.4 mmol). The reaction mixture was then degassed witha stream of nitrogen, cooled to 0 C, and triethylamine (220.4 mmol)added. The solution was then allowed to return to room temperature andsubsequently stirred for 24 h. The solution was then diluted with ethylacetate and washed with water, brine, dried (MgSO₄), the solventsremoved in vacuo, and resulting residue treated with diethyl ether (˜250mL) to give the desired product 64 as a white solid (69%), LCMS[M+H]⁺=540.25.

11-d. Synthesis of2-Deoxy-3,4,6-tri-O-(4-methoxybenzyl)-2-trifluoroacetamido-D-glucopyranose(65)

To a solution of the amine 64 (75.6 mmol) in dry chloroform (400 ml) at0° C. was added diisoproplyethylamine (113.4 mmol) and trifluoroaceticacid (16.0 mL, 113.4 mmol). The resulting reaction mixture was thenstirred for 30 min after which time the reaction was allowed to returnto room temperature and stir for a further 1 h. At this time thereaction was cooled to 0° C. and further diisoproplyethylamine (113.4mmol) and trifluoroacetic acid (113.4 mmol) added, the reaction wasallowed to return to room temperature and stirred for 3 h. The reactionmixture was then poured into dilute sodium hydrogen carbonate and themixture stirred for 30 min. The solid was washed with water, transferredto a flask and dried by co-evaporation with acetonitrile to give thecrude product. Ethyl acetate was then added to the residue and theresulting suspension refluxed for 2 h. Petrol ether (˜300 mL) was thenadded to this, the mixture cooled to room temperature, and the resultingsolid filtered and dried under high vacuum to give the desired product65 as a solid (77%), δ_(H) (400 MHz; CDCl₃) 3.04-3.17 (1H, m), 3.54-3.60(2H, m), 3.61-3.71 (2H, m), 3.79 (3H, s), 3.80 (3H, s), 3.81 (3H, s),4.01 [dt, J 3.0 Hz and J 10.4 Hz] and 4.16 [dt, J 3.7 Hz and J 10.1 Hz](1H), 4.43 (2H, t, J 10.4 Hz), 4.50-4.60 (2H, m), 4.66-4.78 (2H, m),5.23 (1H, d, J 4.0 Hz), 6.11 (1H, br d, J 2.9 Hz), 6.80-6.90 (6H, m),7.06 (2H, d, J 11.1 Hz), 7.18 (2H, d, J 12.6 Hz) and 7.24 (2H, d, J 11.1Hz); LCMS [M+Na]⁺=658.2.

11-f. Formation of Imidate (65)

To a solution of the lactol 11 (8.7 mmol) in tetrahydrofuran (540 mL)was added trichloroacetonitrile (172.9 mmol), followed by potassiumcarbonate (103.9 mmol), and the suspension stirred for 8 days. After 8days the suspension was filtered through celite, washed withtetrahydrofuran and all the solvent removed in vacuo to leave a brownoil. The oil was then purified by column chromatography (eluenttoluene/acetone; 20:1) to give the desired product 12 as a brownsemi-solid (60%).

EXAMPLE 12 Synthesis of Disaccharide and Functionalisation

12-a. Glycosylation with a Trichloroacetimidate Donor to AffordDisaccharide (67)

To a solution of the acceptor 60 (1.8 mmol) and the donor 66 (2.7 mmol)in dry 1,2-dichloroethane (84 mL) was added 3 A acid-washed molecularpellets (4 g) and the resulting mixture stirred for 20 min. To themixture was then added TMSOTf (1.8 mL of a 0.1M solution in dry1,2-dichloroethane, 0.18 mmol) and the reaction then stirred for 15 min.After this time triethylamine (6 mL) was added and the suspensionfiltered, washed with dichloromethane and all solvent removed in vacuoto leave a yellow solid. This resulting solid was triturated with etherand filtered to give the disaccharide 67 as a cream solid (65%), δ_(H)(400 MHz; CDCl₃) 3.26-3.35 (1H, m), 3.42-3.66 (5H, m), 3.68-3.72 (1H,m), 3.74 (3H, s), 3.76 (3H, s), 3.76-3.82 (4H, m), 3.78 (6H, s),3.87-3.96 (1H, m), 4.32-4.54 (6H, m), 4.62-4.79 (3H, m, [4.66, dd, J 3.4Hz and J 13.3 Hz]), 5.02 (1H, dd, J 3.8 Hz and J 12.6 Hz), 5.04 (1H, d,J 10.7 Hz), 6.34 (1H, d, J 10.3 Hz), 6.76-6.92 (8H, m), 7.07 (4H, dd, J1.6 Hz and J 9.0 Hz), 7.20-7.24 (4H, m), 7.69-7.74 (2H, m) and 7.77-7.85(2H, m); LCMS [M+H+Na]⁺=1078.2.

12-b. Amine Deprotection to Afford the Diamine Derivative (68)

The protected disaccharide 67 (0.95 mmol) was suspended inn-butanol/ethylenediamine (1:1, 14 mL) and heated at reflux for 16 h.The solvent was then removed in vacuo, and the residue taken up inchloroform, washed with dilute brine, dried (MgSO₄), and solvent removedin vacuo to leave an oil. The oil was purified by column chromatography(eluent 10:1, chloroform/methanol) to give the desired product 68 as agummy solid [72%, used directly in next step[, δ_(H) (400 MHz; CDCl₃)2.91 (1H, dd, J 8.2 and J 10.3 Hz), 2.96-3.08 (1H, m), 3.21-3.29 (1H,m), 3.35-3.50 (4H, m), 3.52-3.68 (5H, m), 3.74-3.82 (12H, singlets),3.91-3.98 (1H, m), 4.16 {1H, (d, J 3.6 Hz) and 4.32 (d, J 7.8 Hz)},4.35-4.52 (7H, m), 4.58-4.64 (1H, m), 4.71 {1H, (d, J 10.3 Hz) and 4.91(d, J 10.9 Hz)}, 6.80-6.92 (8H, m), 7.11 (2H, d, J 8.8 Hz), 7.2-7.32(6H, m); LCMS [M+H⁺]=830.35.

12-c. Urea Formation (69)

Compound 69 was prepared according to the procedure described in GeneralMethod 1, yield [30%, used directly in next step], LCMS [M+H]⁺=1204.53.

12-d. Azide Reduction (70)

Compound 70 was prepared according to the procedure described in GeneralMethod 3 [99%, used directly in next step], LCMS [M+H]⁺=1178.65.

12-e. Lipid HBTU Coupling (71)

Compound 71 was prepared according to the procedure described in GeneralMethod 4, LCMS [M+H]⁺=1374.83.

12-f. Global Deprotection (72)

Compound 72 was prepared according to the procedure described in GeneralMethod 5, [30%, yield over two steps from compound 70] as a white solid;LCMS [M+H]⁺=894.22.

EXAMPLE 13 Synthesis of an Aminoacid Linked Lipidic Side Arm

13-a. DIC Coupling of a Aminoacid Side Arm (73)

Compound 73 (using 0.034 mmol of 70) was prepared according to theprocedure described in General Method 7; HPLC Method A, Rt=7.5 min,[M+H]⁺=1475.

13-b. Deprotection of the Boc Protected Amine and 4-Methoxybenzyl Groups(74)

Compound 74 was prepared according to the procedure described in GeneralMethod 5; HPLC Method A, Rt=4.82 min, [M+H]⁺=895.

13-c. DIC Coupling of a Lipidic Side Arm (75)

Compound 75 was prepared according to the procedure described in GeneralMethod 7; HPLC-Method A, Rt=6.18 mins, [M+H]⁺=1117; RT=7.16 min,[M+H⁺]=1147.

13-d. Ester Hydrolysis to Provide the Free Acid (76)

Compound 75 was prepared according to the procedure described in GeneralMethod 8, yield 25.7% from 70; HPLC Method A, Rt=4.75 min, [M+H]⁺=939.

EXAMPLE 14 Synthesis of an Aminoacid Linked Lipidic Side Arm-2

14-a. DIC Coupling of a Aminoacid Side Arm (77)

Compound 77 was prepared (using 0.034 mmol of 70) according to theprocedure described in General Method 7, HPLC Method A, Rt=7.3 mins,[M+H]⁺=1497.

14-b. Deprotection of the Boc Protected Amine and 4-Methoxybenzyl Groups(78)

Crude 77 was stirred at room temperature in DCM (2 mL), TFA (40 μL) andTES (100 μL) for 2 hrs. The reaction mixture was concentrated in vacuo,HPLC Method A, Rt=4.5 mins, [M+H]⁺=917.

14-c. DIC Coupling of a Lipidic Side Arm (79)

Compound 79 was prepared according to the procedure described in GeneralMethod 7; HPLC Method A, Rt=5.15 mins, [M+H]⁺=1014.

14-d. Ester Hydrolysis to Provide the Free Acid (80)

Compound 79 was prepared according to the procedure described in GeneralMethod 8, yield (from 70) 24.5%; HPLC-Method A, Rt=4.50 mins,[M+H]⁺=925.

EXAMPLE 15 Synthesis of2-deoxy-2-(3-trifluoromethyl)-ureido-β-D-glucopyranosyl1,5-anhydro-2,4-dideoxy-4-(1-decanesulphonamido)-2-(3-trifluoromethyl)-ureido-D-galactitol4 with a Sulphonamide Lipidic Side Arm

15-a. Formation of a Sulphonamide Linked Lipidic Side Arm (82)

To a solution of compound 70 (0.034 mmol) and pyridine (36.4 equiv) indry dichloromethane (1 ml) was added 81 (20 equiv) in several portions.The resulting reaction mixture was stirred under nitrogen atmosphere for2 hr and saturated sodium bicarbonate solution (20 ml) added. After 30min stirring, the aqueous phase was extracted with dichloromethane; thecombined organic solutions were dried over MgSO₄ and evaporated in vacuoto dryness. The residue was purified by preparative TLC (eluent: neatEtOAc) to furnish the crude2-deoxy-3,4,6-tri-O-(4-methoxybenzyl)-2-(3-trifluoromethyl)-ureido-β-D-glucopyranosyl1,5-anhydro-2,4-dideoxy-6-(4-methoxybenzyl)-4-(1-decanesulphonamido)-2-(3-trifluoromethyl)-ureido-D-galactitol82 (HPLC Method A, Rt=7.71 mins, [M+H]⁺=1382.4). The product was usedfor the next step without further purification.

15-b. Global Deprotection to Provide the Final Product (83)

Compound 83 was prepared according to the procedure described in GeneralMethod 5, (10.8% from 70) HPLC Method A, Rt=11.85 mins, [M+H]⁺=902.53)

EXAMPLE 16 Synthesis of2-deoxy-2-(3-trifluoromethyl)-ureido-β-D-glucopyranosyl1,5-anhydro-2,4-dideoxy-4-(1-decylphosphonamido)-2-(3-trifluoromethyl)-ureido-D-galactitol7

16-a. Formation of a Phosphonamide Linked Lipidic Side Arm (85)

To a solution of 1-decylphosphonic acid (1 mmol) and dimethylformamide(1.7 μl) in dry dichloromethane (4 ml) was added drop-wiseoxalylchloride (261.2μl, 3 mmol). The resultant solution was stirred atroom temperature under nitrogen atmosphere for 1 hr and evaporated todryness in vacuo. The residue was dried under high vacuum for 1 hr toafford compound 84 as brownish liquid. To a 84 (1 mmol) in DCM (4 ml)was added triethylamine (695 μl, 5 mmol) followed by compound 70 [0.034mmol]. The resultant reaction mixture was stirred under nitrogenatmosphere for 1 hr and 1N hydrochloride solution (20 ml) added; theaqueous phase was extracted with dichloromethane (3×20 ml); the combinedorganic solutions were dried over MgSO4 and evaporated in vacuo todryness. The product was used for the next step without furtherpurification. (HPLC Method A, Rt=7.67 min, [M+H]⁺=1382.82).

16-b. Global Deprotection to Provide the Final Product (66)

Compound 86 was prepared according to the procedure described in GeneralMethod 5, yield 8% (from 70); HPLC Method A, Rt=5.36 mins, [M+H]⁺=902.5)

EXAMPLE 17 Synthesis of2-deoxy-2-(3-trifluoromethyl)-ureido-β-D-glucopyranosyl1,5-anhydro-2,4-dideoxy-4-(N-octanoylglycylamido)-2-(3-trifluoromethyl)-ureido-D-galactitol

17-a. DIC Coupling to Form an Amide Linked Lipidic Side Arm (88)

Compound 88 was prepared (from 0.034 mmol of 70) according to theprocedure described in General Method 7. The crude 88 was used for thenext step without further purification; HPLC Method A, Rt=7.17 min;[M+H]⁺=1361.80,

17-b. Global Deprotection to Provide the Final Product (89)

Compound 89 was prepared according to the procedure described in GeneralMethod 5, yield 24% (from 70); HPLC Method A, Rt=4.86 mins;[M+H]⁺=881.36.

EXAMPLE 18 Synthesis of2-deoxy-2-(3-trifluoromethyl)-ureido-β-D-glucopyranosyl1,5-anhydro-2,4-dideoxy-4-(N-octanoyl-N′-yl-3,4-dioxo-cyclobutene-1,2-diamine)-2-(3-trifluoromethyl)-ureido-D-galactitol92

18-a. Coupling of Diethyl Squarate to Form a Vinylogous Amide (90)

Amine 70 (0.034 mmol) was dissolved in Ethanol and DIPEA (35 mmol) anddiethylsquarate (70 μmol) was added. After stirring at room temperaturea complete conversion of the starting material to 5 was observed; HPLCMethod A, Rt=6.70 mins; [M+H]⁺=1302.47.

18-b. Coupling of an Alkylamine Side Chain to the Squarate (91)

Decylamine (100 μmol) was added in the mixture (from 18-a) and heated to50° C. over night. The mixture was diluted with ethyl acetate, washedtwice with 10% citric acid, satd. sodium bicarbonate solution, and thesolvents removed in vacuo. The crude 91 was used without furtherpurification in the next step; HPLC Method A, Rt=7.66 mins,[M+H]⁺=1413.15.

18-c. Global Deprotection to Provide the Final Product (92)

Compound 86 was prepared according to the procedure described in GeneralMethod 5 to give pure 92, yield 26.2% (from 70); HPLC Method A, Rt=5.61ml; [M+H]⁺=933.32.

EXAMPLE 19 Synthesis of2-deoxy-2-(3-trifluoromethyl)-ureido-5-D-glucopyranosyl1,5-anhydro-2,4-dideoxy-4-((N-hexanoyl)-4-amino-butyroyl)-2-(3-trifluoromethyl)-ureido-D-galactitol10

19-a. DIC Coupling to Form an Amide Linked Lipidic Side Arm (94)

Compound 94 was prepared (from 0.034 mmol of 70) according to theprocedure described in General Method 7; HPLC Method A, Rt=6.85 min;[M+H]⁺=1361.47. The crude product was directly used for the next step.

19-b. Global Deprotection to Provide the Final Product (95)

Compound 95 was prepared according to the procedure described in GeneralMethod 5, to give pure 10, yield 42.1% (from 70); HPLC Method A, Rt=4.60min; [M+H]⁺=881.39.

EXAMPLE 20 Synthesis of a Disaccharide with a Lipidic Side Chain andAcid Function

NB. Reaction series was completed separately for both the R and the Sisomers.

20-a. DIC Coupling to Form an Amide Linked Lipidic Side Arm (96)

Compound 96 was prepared according to the procedure described in GeneralMethod 7, the crude product was directly used for the next step; HPLCMethod A, Rt=7.70 mins; [M+H]⁺=1585.45.

20-b and 20-c. Fmoc Deprotection Followed by Amide Formation (98)

Compound 98 was prepared according to the procedure described in GeneralMethod 9, the crude product was directly used for the generaldeprotection, (HPLC Method B, Rt=18.51 mins, [M+H]⁺=1489.77).

20-d. Global Cleavage to Afford the Final Product

Compound 99 was prepared according to the procedure described in GeneralMethod 5, yield (R isomer) 27.5% from 70. yield (S isomer) 10.5% from70; HPLC Method A, Rt=4.88 mins; [M+H]⁺=953.46

EXAMPLE 21 Synthesis of a Disaccharide with a PEG Side Chain

21-a. DIC Coupling to Form an Amide Linked PEG Side Arm (100)

Compound 100 was prepared according to the procedure described inGeneral Method 7; HPLC Method A, Rt=6.81 mins; [M+H]⁺=1338.49. The crudeproduct was directly used for the next step.

21-b. Global Cleavage to Afford the Final Product (101)

Compound 101 was prepared according to the procedure described inGeneral Method 5 (101 purified by preparative chromatography on a C18column), yield 21.8% (from 70); HPLC Method A, Rt=4.27 min;[M+H]⁺=958.52.

EXAMPLE 22 Synthesis of a Range of Lipid Conjugates

22-a. Preparation of Amido Derivatives at C-4 (102a, 102b, 102c, 102e)

Compounds 102a, 102b, 102c, 102e were prepared according to theprocedure provided in General Method 4.

22-b. Reaction with Acetic Anhydride (102d)

Added dropwise to a solution of the sugar amine (0.04 mmol) In drydichloromethane (0.4 mL) was acetic anhydride (0.12 mmol) and thesolution stirred for 16 h. Chloroform (15 mL) was then added and washedwith water, 10% citric acid, saturated sodium hydrogen carbonate, brine,dried (MgSO₄) and the solvent removed under reduced pressure to give thetitle compound 5 quantitatively as an oil, LCMS [M+H]⁺=1220.5.

22-c. Global Cleavage to Afford the Final Product (103a-103e)

Compound 103a-e were prepared according to the procedure described inGeneral Method 5.

TABLE 1 Derivatives prepared in Example 22.

Comp. No. R1 R2 Molecular ion Yield 102a R1a R2a [M + H]⁺ = 1276.2 87%102b R1b R2a [M + H]⁺ = 1374.2 Quant. 102c R1c R2a [M + H]⁺ = 1358.3Quant. 102d R1d R2a [M + H]⁺ = 1220.5 Quant. 102e R1e R2a [M + H]⁺ =1346.5 Quant. 103a R1a R2b [M + H]⁺ = 796.3 50% 103b R1b R2b [M + H]⁺ =894.3 49% 103c R1c R2b [M + H]⁺ = 878.3 30% 103d R1d R2b [M + H]⁺ =740.1 30% 103e R1e R2b [M + H]⁺ = 866.2 41% Side Arms for Table 1.

EXAMPLE 23 Synthesis of a Further Disaccharidic Library

Part 1: Preparation of Compounds 111-01 to 111-30

Part 2: Preparation of Compound 113-01 to 113-03

Part 3: Preparation of Compounds 114-01-114-03 for the Synthesis ofAlternate Urea Building Blocks For the Preparation of FurtherDerivatives at R₃ as Exemplified by Structures 117-01-117-15 (byemploying 5 different lipidic side chains).

TABLE 2 Experimental Results, Intermediates and Products for Example 23

Rt Yield Product SM* M^(§) R1 R2 R3 R4 [M + X]⁺ (min)^(‡) %  68  67 10 II L K [M + H]⁺ = 830.5 6.07   74.8 104  67 10 I I M K [M + H]⁺ = 804.55.36 18 105  68 11 H I L K [M + H]⁺ = 1052.52  8.0-12.0 32 106-01 105 15H N L K [M + H]⁺ = 1094.6 6.90 100  106-02  68 11 H H L K [M + H]⁺ =1274.7 7.66   19.5 106-03 105  4 H C L K [M + H]⁺ = 1224.7 7.32 84106-04 105 14 H D L K [M + Na]⁺ = 1228.6 7.45 100  106-05 105  1 H E L K[M + Na]⁺ = 1261.7 7.38 78 106-06 105 14 H F L K [M + H]⁺ = 1205.7 7.3598 106-07 105 13 H G L K [M + Na]⁺ = 1208.8 7.43 82 107-01 106-03  3 H CM K Detected in 108-01 form 100  107-02 106-04  3 H D M K Detected in108-02 form 96 107-03 106-05  3 H E M K Detected in 108-03 form 100 107-04 106-06  3 H F M K Detected in 108-04 form 100  107-05 106-07  3 HG M K Detected in 108-05 form 100  108-01 107-01 15 H C B K [M + H]⁺ =1240.7 6.99 100  108-02 107-02 15 H D B K [M + H]⁺ = 1222.7 7.07 90108-03 107-03 15 H E B K [M + H]⁺ = 1255.5 6.99 100  108-04 107-04 15 HF B K [M + H]⁺ = 1221.3 7.42 86 108-05 107-05 15 H G B K [M + Na]⁺ =1224.8 7.05 95 108-06 107-01  4 H C A K [M + H]⁺ = 1366.9 8.09 85 108-07107-02  4 H D A K [M + H]⁺ = 1348.9 8.01   67.7 108-08 107-03  4 H E A K[M + H]⁺ = 1381.9 8.33 88 108-09 107-04  4 H F A K [M + H]⁺ = 1347.47.86 100  108-10 107-05  4 H G A K [M + H]⁺ = 1328.6 8.18 100  109-01108-06 16 I C A K Detected in 110-02 form 67 109-02 108-07 16 I D A KDetected in 110-03 form 61 109-03 108-08 16 I E A K Detected in 110-04form 90 109-04 108-09 16 I F A K Detected in 110-05 form 58 109-05108-10 16 I G A K Detected in 110-06 form 51 110-01  68 15 N N L K [M +H]⁺ = 914.5 5.71 100  110-02 109-01 15 N C A K [M + H]⁺ = 1186.76 7.50100  110-03 109-02 15 N D A K [M + H]⁺ = 1168.77 7.54 100  110-04 109-0315 N E A K [M + H]⁺ = 1201.8 7.33 100  110-05 109-04 15 N F A K [M + H]⁺= 1167.5 7.30 100  110-06 109-05 15 N G A K [M + H]⁺ = 1148.5 7.51 100 110-07 109-01  4 C C A K [M + H]⁺ = 1316.7 7.59   86.8 110-08 109-02  4C D A K [M + H]⁺ = 1298.6 7.94 100  110-09 109-03  4 C E A K [M + H]⁺ =1331.71 7.90 100  110-10 109-04  4 C F A K [M + H]⁺ = 1297.5 7.58 100 110-11 109-05  4 C G A K [M + H]⁺ = 1278.7 7.82 100  110-12 109-01 14 DC A K [M + H]⁺ = 1298.5 7.68   84.7 110-13 109-02 14 D D A K [M + H]⁺ =1280.4 7.92 100  110-14 109-03 14 D E A K [M + H]⁺ = 1313.83 8.03 100 110-15 109-05 14 D G A K [M + H]⁺ = 1260.5 7.89   28.2 110-16 109-01  1E C A K [M + Na]⁺ = 1353.8 7.86 100  110-17 109-02  1 E D A K [M + H]⁺ =1313.81 7.81 100  110-18 109-04  1 E F A K [M + H]⁺ = 1312.8 7.64 100 110-19 109-05  1 E G A K [M + H]⁺ = 1293.8 7.88 100  110-20 109-01 12 FC A K [M + H]⁺ = 1297.9 7.60 80 110-21 109-02 12 F D A K [M + H]⁺ =1279.8 7.92 77 110-22 109-03 12 F E A K [M + H]⁺ = 1312.84 7.65 100 110-23 109-04 12 F F A K [M + H]⁺ = 1278.8 7.73 73 110-24 109-05 12 F GA K [M + H]⁺ = 1259.9 7.64 70 110-25 109-01 13 G C A K [M + H]⁺ = 1278.87.64 66 110-26 109-02 13 G D A K [M + H]⁺ = 1260.8 7.91 75 110-27 109-0313 G E A K [M + H]⁺ = 1293.87 7.96 100  110-28 109-04 13 G F A K [M +H]⁺ = 1259.8 7.75 72 110-29 109-05 13 G G A K [M + H]⁺ = 1240.8 7.67 80110-30 109-03  1 O E A K Compound fragments to 110-31 100  under LCMSconditions 110-31 P E A K [M + H]⁺ = 1202.81 7.26 111-01 110-07  5 C C AI [M + H]⁺ = 836.4 5.33 100  111-02 110-08  5 C D A I [M + H]⁺ = 818.45.57 100  111-03 110-09  5 C E A I [M + H]⁺ = 851.5 5.43 100  111-04110-10  6 C F A I [M + H]⁺ = 817.4 5.44 18 111-05 110-11  5 C G A I [M +H]⁺ = 798.5 5.54 100  111-06 110-12  5 D C A I [M + H]⁺ = 818.4 5.56100  111-07 110-13  4 D D A I [M + H]⁺ = 800.4 5.47 100  111-08 110-14 5 D E A I [M + H]⁺ = 833.4 5.83 100  111-09 110-15  5 D G A I [M + H]⁺= 780.4 5.41 100  111-10 110-16  5 E C A I [M + H]⁺ = 851.3 5.64 100 111-11 110-17  5 E D A I [M + H]⁺ = 833.3 5.75 100  111-12 110-18  5 E FA I [M + H]⁺ = 832.5 5.53 16 111-13 110-19  5 E G A I [M + H]⁺ = 813.35.69 100  111-14 110-20  6 F C A I [M + H]⁺ = 817.4 5.49 51 111-15110-21  6 F D A I [M + H]⁺ = 799.4 5.46 48 111-16 110-22  5 F E A I [M +H]⁺ = 832.5 5.65  2 111-17 110-23  6 F F A I [M + H]⁺ = 798.4 5.36 20111-18 110-24  6 F G A I [M + H]⁺ = 779.5 5.58 53 111-19 110-25  5 G C AI [M + H]⁺ = 798.5 5.30 100  111-20 110-26  5 G D A I [M + H]⁺ = 780.55.57 100  111-21 110-27  5 G E A I [M + H]⁺ = 813.4 5.69 100  111-22110-28  6 G F A I [M + H]⁺ = 779.5 5.08 10 111-23 110-29  5 G G A I [M +H]⁺ = 760.5 5.28 100  111-24 108-06  5 H C A I [M + H]⁺ = 886.55 6.07100  111-25 108-07  5 H D A I [M + H]⁺ = 868.58 5.99 100  111-26 108-08 5 H E A I [M + H]⁺ = 901.4 6.00 100  111-27 108-09  6 H F A I [M + H]⁺= 867.6 6.03 20 111-28 108-10  5 H G A I [M + H]⁺ = 848.6 5.91 100 111-29 110-30  5 P E A I [M + H]⁺ = 722.4 4.63 100  111-30 109-03  5 I EA I [M + H]⁺ = 679.5 4.62 100  112-01 104 15 N N B K [M + Na]⁺ = 952.75.01 47 112-02 104  4 C C Q K [M + H]⁺ = 1320.5 6.99 76 112-03 104  1 EE R K [M + H]⁺ = 1365.4 7.21 92 113-01 112-01  5 N N B I [M + H]⁺ =450.26 0.69 100  113-02 112-02  5 C C Q I [M + H]⁺ = 840.4 4.53 100 113-03 104  5 I I M I [M + H]⁺ = 324.2 0.62 100  114-01  68  1 S S L K[M + H]⁺ = 1204.9 7.02 100  114-02  68  1 T T L K [M + H]⁺ = 1096.5 6.82100  115-03  68  1 U U L K [M + H]⁺ = 1204.3 7.25 100  111-01-1 111-0117 C C A I As Start Material N/A 43 111-02-1 111-02 17 C D A I As StartMaterial N/A   19.2 111-06-1 111-06 17 D C A I As Start Material N/A  34.5 111-07-1 111-07 17 D D A I As Start Material N/A 51 111-08-1111-08 17 D E A I As Start Material N/A 27 111-10-1 111-10 17 E C A I AsStart Material N/A 16 111-11-1 111-11 17 E D A I As Start Material N/A75 111-29-1 111-29 17 P E A I As Start Material N/A 45 SM* = StartingMaterial M^(§) = Method of Synthesis (General Method) Rt (min)^(‡): Allcompounds in Table 2 were analysed by HPLC Method A. Note: Under theemployed analytical conditions, compounds containing amino group(compounds classed as 68, 104, 105, 107, 109) elute in unusual broadpeaks, sometimes several minutes wide; therefore, most of the time theyare detected as acetamide derivatives obtained via acylating with aceticanhydride.] Substituents for Table 2

HPLC Methods. HPLC Method A

Flow Rate Time H₂O % MeCN % mL/min 0 95 5 2 1 95 5 2 7 0 100 2 12 0 1002

Agilent SB Zorbax C18 4.6×50 mm (5 μm, 80 Å)

LC Mobile Phase: Acetonitrile:Water 0.1% formic acid

HPLC Method B

Flow Rate Time H₂O % MeCN % mL/min 0.00 95 5 1.00 95 5 20.00 0 100

Agilent SB Zorbax C18 4.6×50 mm (5 μm, 80 Å)

LC Mobile Phase: Acetonitrile:Water 0.1% formic acid

EXAMPLE 24 Synthesis of an Alpha 1→4 Linked Disaccharidic CompoundSelective Removal of Protecting Groups for Diversity-Part 1

24-a: Glycosylation

Compound 118 [1.0 mmol] and 60 [1.5 mmol] were dissolved in drydichloromethane [16 mL] and stirred with molecular sieves [4 Å acidwashed] at room temperature for 1 h. To the mixture was then added2,6-di-tert.-butylpyridine [1.6 mmol] and DMTST [1.6 mmol], and thereaction stirred at room temperature. After 2.5 h further 60 [0.2 mmol],2,6-di-tert.-butylpyridine [0.2 mmol] and DMTST [0.2 mmol] were addedand the reaction stirred at room temperature for 1 h. The reaction wasthen quenched with triethylamine, the solvents were removed in vacuo andthe product purified by column chromatography (silica, petrolether/ethylacetate 2:1) to give 119 as a colourless foam [63%]; HPLC Method A,Rt=8.09 mins, [M+Na]⁺=1087.56; 1H-NMR (CDCl₃): 8.00 (d, 2H, Ar),7.82-7.65 (m, 2H, Ar), 7.95-7.14 (m, 19H, Ar), 6.90 (d, 2H, Ar), 5.52(dd, 1H, H-2′, J1′-2′=3.4 Hz, J2′-3′=10.1 Hz), 5.24 (d, 1H, H1′), 4.82(s, 1H, CHPh), 4.72-4.63 (m, 2H), 4.54 (dd, 1H, H-3′, J3′-4′=3.6 Hz),4.38 (AB, 2H, CH₂Ar, Jgem=11.7 Hz), 3.95-3.86 (m, 2H), 3.83 (s, 3H,OCH₃), 3.83-3.76 (m, 1H), 3.62-3.56 (m, 1H), 3.49 (dd, 1H, J=5.9 Hz,J=9.0 Hz), 3.38 (dd, 1H, J=7.7 Hz, J=9.2 Hz), 3.37 (dd, 1H, H4′,J4′-5′<1 Hz), 3.30 (dd, 1H, H1-a, Jgem=12.5 Hz. J1a,2=1.9 Hz), 3.25 (m,1H), 2.92 (dd, 1H, H-1b, J1b,2<1 ), 0.88 (s, 9H, tBu),

24-b: Azide Reduction

Compound 119 [0.164 mmol] was treated according to the proceduredescribed in General Method 3 (NB: compound smears over several minuteson HPLC column (HPLC Method A); [M+H]⁺=1039.53. The solution of thecrude product 120 was directly used for the next conversion.

24-c: Amide Coupling

Crude 120 was treated with undecanoic acid 120 mg [0.65 mmol] accordingto the procedure described by General Method 7. 1 The residue containing121 was purified on a silica column (gradient petrolether/ethyl acetate2:1 to petrolether/ethyl acetate 1:1 with 2% triethylamine) to give 121[51%]; HPLC Method A, Rt=9.14 mins; [M+Na]⁺=1229.69, and unreacted 120(31%).

24-d: Silylether Cleavage

To a solution of 121 in DMF [3 mL], was added a 1 molar solution of TBAFin THF [0.5 mL] and acetic acid [30 μL], and the mixture heated to 65°C. for 6 h. The reaction mixture was diluted with ethyl acetate and thesolution washed with saturated sodium bicarbonate solution and water,the dried over magnesium sulfate and the solvents removed in vacuo togive crude 122 (100% conversion by ELSD); HPLC Method A, Rt=7.17 mins;[M+H]⁺=969.55.

24-e to e2: Removal of Acid Labile Protecting Groups

(24-e1) Crude 122 was dissolved in dry dichloromethane [5 mL] andtriethylsilane [0.5 mL] and trifluoroacetic acid [0.1 mL] were added.After stirring at room temperature for 10 min conversion to 123a wascomplete (HPLC Method A, Rt=6.80 min, [M+H]⁺=849.50). (24-e2). Furtherstirring at room temperature for 3 h gave 123 (100% conversion by ELSD);HPLC Method A, Rt=6.71 mins; [M+H]⁺=761.43.

Selective Removal of Protecting Groups for Diversity-Part 2

24-f1 to f2: Removal of Acid Labile Protecting Groups

(24-f1). Compound 121 [8 μmol] was dissolved in dry dichloromethane [1mL] and triethylsilane [0.1 mL] and trifluoroacetic acid [0.02 mL] wereadded. After stirring at room temperature for 2 min conversion to 124awas complete (HPLC Method A, Rt=8.54 mins, [M+H]⁺=1187.49). (24-f2).Further stirring at room temperature for 3 hrs gave 124 (100% conversionby ELSD); HPLC Method A, Rt=7.87 mins, [M+H]⁺=999.56.

Selective Removal of Protecting Groups for Diversity-Part 3

24-g: Phthalimido Cleavage

To a solution of 121 [0.10 mmol] in ethanol [5 mL] was added hydrazinehydrate [0.05 mL] and the solution refluxed for 20 h. The solvents wereremoved in vacuo and the residue co-evaporated with toluene to givecrude 125 (100% conversion by ELSD). Product smears over several minuteson HPLC (HPLC Method A), [M+H]⁺=1077.43.

24-g: Sulfonamide Formation

Compound 125 [1.8 μmol] was reacted with tosylchloride [5 mg] accordingto General Method 14 to give 126 (100% conversion by ELSD), HPLC MethodA, Rt=9.25 mins; [M+H]⁺=1231.65, [M+Na]⁺=1253.63.

Selective Removal of Protecting Groups for Diversity-Part 4

24-i: Urea Formation

Compound 125 [0.10 mmol] was reacted with 3-trifluoromethylphenylisocyanate [0.4 mmol] according to General Method 1 to afford 127 (73%purity by ELSD); HPLC Method A, Rt=9.04 mins; [M+H]⁺=1264.75.

24-j: Ester Cleavage

Compound 127 [0.10 mmol] was treated according to the proceduredescribed in General Method 2 (with the exception that only MeOH wasused as solvent) to afford crude 128; HPLC Method A, Rt=8.60 mins;[M+H]⁺=1126.48, [M+H]⁺=1148.46.

24-k: Carbamate Formation

To a solution of 128 [0.10 mmol] in dry DMF [5 mL], was added3-trifluoromethylphenyl isocyanate [0.4 mmol] and DBU [45 μL], and thesolution heated to 80° C. for 20 h. The reaction mixture was dilutedwith ethyl acetate, washed with saturated sodium bicarbonate solutionand water, dried over magnesium sulfate, and the solvents removed invacuo to give 129.

24-l: Silylether Cleavage

To a solution of 129 in DMF [3 mL], was added a 1M solution of TBAF inTHF [0.5 mL] and acetic acid [30 μL], and the reaction mixture heated to65° C. for 6 h. The reaction mixture was diluted with ethyl acetate andthe solution washed with saturated sodium bicarbonate solution, water,dried over magnesium sulfate, and the solvents removed in vacuo to givecrude 130.

24-m1 to 24-m2: Removal of Acid Labile Protecting Groups

(24-m1). To a solution of compound 130 in dichloromethane [5 mL] wasadded triethylsilane [0.5 mL] and trifluoroacetic acid [0.1 mL]. Afterstirring at room temperature for 2 min conversion to 131a was complete,(24-m2). Further stirring at room temperature for 3 hrs gave 131quantitatively.

Selective Removal of Protecting Groups for Diversity-Part 5

24-n: Silylether Cleavage

To a solution of 127 in DMF [3 mL], was added a 1M solution of TBAF inTHF [0.5 mL] and acetic acid [30 μL], and the mixture heated to 65° C.for 6 h. The reaction mixture was then diluted with ethylacetate and thesolution washed with saturated sodium bicarbonate solution, water, driedover magnesium sulfate, and the solvents removed in vacuo to give crude132.

24-o: Carbamate Formation

To a solution of 132 [0.10 mmol] in DMF [5 mL] was added3-trifluoromethylphenyl isocyanate [0.4 mmol] and DBU [45 μL], and thesolution heated to 80° C. for 20 h. The reaction mixture was dilutedwith ethyl acetate, washed with saturated sodium bicarbonate solution,water, dried over magnesium sulfate, and the solvents removed in vacuoto give 133.

24-p: Ester Cleavage

Compound 133 [0.10 mmol] was treated according to General Method 2 (withthe exception that only MeOH was used as solvent) to provide crude 134.

24-q1 to 24-q2: Removal of Acid Labile Protecting Groups

(24-q1). Compound 134 was dissolved in dry dichloromethane [5 mL] andtriethylsilane [0.5 mL] and trifluoroacetic acid [0.1 mL] were added.After stirring at room temperature for 2 min conversion to 135a wascomplete. (24-q2). Further stirring at room temperature for 3 hrs gave135.

EXAMPLE 25 Synthesis of a Beta 1→6 Linked Disaccharidic Compound forDrug Discovery-1

25-a: Glycosylation

To a solution of 60 [0.48 mmol] and 136 [0.70 mmol] in dichloroethane [8mL] was added DMTST [0.48 mmol], and the mixture stirred for 45 mins atroom temperature. At that time further DMTST [0.21 mmol] was added, andafter stirring for 20 mins the reaction was quenched by the addition oftriethylamine [0.5 mL]. The reaction mixture was then diluted withdichloromethane, washed with 10% citric acid, saturated sodiumbicarbonate solution, dried over magnesium sulfate, the solventsevaporated in vacuo and the product purified by column chromatography(silica, petrol ether/ethyl acetate 1:1) to give 137 as a colorless foam[59%]; HPLC Method A, Rt=5.06 mins: [M+Na]⁺=758.49.

25-b: Acetylation

To a solution of 137 [2 mg] in pyridine [0.2 ml] was added aceticanhydride [50 μL], and the ensuing reaction mixture stirred at roomtemperature for 2 hrs. The reaction mixture was then diluted withdichloromethane and washed with 10% citric acid, saturated sodiumbicarbonate solution, dried over magnesium sulfate and the solventsevaporated in vacuo to give 138; ¹H-NMR (CDCl₃): 7.85-7.62 (m, 8H, Ar),5.75 (dd, 1H, H-3′, J_(2′,3′)=10.4 Hz, J_(3′,4′)=8.8 Hz), 5.70 (dd, 1H,H-3, J_(2,3)=11.0 Hz, J_(3,4)=3.4 Hz), 5.39 (d, 1H, H-1′, J_(1′,2′)=8.7Hz), 5.12 (dd, 1H, H-4′, J_(4′,5′)<1 Hz), 4.64 (ddd, 1H, H-2), 4.25 (dd,1H, H-2′), 4.00 (dd, 1H, H-4), 3.88-3.76 (m, 3H, H-1a, H-5, H-5′),3.70-3.52 (m, 5H, H-1b, H-6a, H-6b, H-6a′, H-6b′), 2.07, 1.98, 1.87,1.71 (each s, 3H, Ac).

EXAMPLE 26 Synthesis of a Beta 1→46 Linked Disaccharidic Compound forDrug Discovery-2

26-a. Formation of a Beta 1→6 Linked Disaccharide

A solution of thioglycoside 139 [0.154 mmol], trichloroacetimidate 66[1.5 eq. with respect to thioglycoside] and 4 angstrom molecular sieves[0.26 g] in 1,2-DCE [2.6 mL] was stirred at room temperature for 15mins. At this time TMSOTf [0.3 eq.] was added. The reaction was allowedto stir for 30 mins at which time it was quenched by the addition oftriethylamine [2 mL]. The reaction mixture was diluted with DCM,filtered and the resulting filtrate concentrated in vacuo to afford aresidue. The residue was purified by column chromatography[toluene/acetone, 20:1] to provide the product as a colourless foam[58%]; HPLC Method A, Rt=8.02 mins; [M+Na]⁺=1316; ¹H-NMR, CDCl₃ δ 4.07(d, 1-H, H-1a J_(1,2)=9.2 Hz), 4.42 (d, 1-H, H-1b, J_(1,2)=8.2 Hz)indicating two beta linkages.

EXAMPLE 27 Synthesis of a Methyl Glycoside Disaccharide for DrugDiscovery

27-a. Benzoylation of the 3-OH Position

To a solution of 141 [37.2 mmol] in 1,2-dichloromethane [140 mL] at 0°C. was added DMAP [2 eq.] and benzoyl chloride [1.5 eq.]. The reactionmixture was allowed to return to room temperature, and stirred for 2hrs. Methanol was added and the reaction mixture was stirred for afurther 15 mins. The reaction mixture was then diluted with CHCl₃,washed with 10% citric acid solution, saturated NaHCO₃ solution,saturated brine solution, dried (MgSO₄), concentrated in vacuo. Compoundwas passed through a plug of silica to give 142 and used directly in thenext step without further purification.

27-b. Benzylidene Cleavage

To a solution of thioglycoside 142 [36.7 mmol] in a mixture ofMeCN/MeOH/H₂O [2:1:0.1, 155 mL] was added p-toluenesulphonic acid [200mg]. The resulting reaction mixture was stirred at 75° C. for 2 hrs. Thereaction was allowed to cool, to room temperature, water was added [50mL] and the volatile solvents [MeCN and MeOH] removed in vacuo. Theresulting suspension was filtered and the collected solid washed furtherwith water followed by petroleum ether and then dried under vacuum toafford pure 143 [98%]; [M+H]⁺=480.3, (99.8% pure by ELSD); HPLC MethodA, Rt=3.80 mins.

27-c. Sialyl Protection of a 6-OH Group

To a suspension of the dial 143 [10 mmol] in pyridine [20 mL] was addedimidazole [1 mmol] and the resulting reaction mixture was then heated to120° C. At this time TBDPS-Cl [12 mmol] was added in portions and thereaction was stirred for 1 hr at 120° C. After this time furtherTBDPS-Cl [0.4 eq.] was added and the reaction was allowed to stir for afurther hour. The reaction mixture was then cooled, and the volatilesremoved in vacuo. The residue was taken up in DCM and washed with 1molar HCl solution, dried (MgSO₄) and the solvent removed in vacuo. Theresidue was washed with petroleum ether to afford pure 144 as a whitesolid [99%]; HPLC Method A Rt=6.66 mins (100% purity by ELSD);[M+H]⁺=718.57.

27-d. Formation of a 4-O-Triflate

To a solution of 144 [2 mmol] in DCM [20 mL] was added pyridine [4 mmol]and the resulting mixture cooled to 0° C. At this time triflic anhydride[3.2 mmol] was slowly added and the reaction mixture was then allowed toreturn to room temperature. The reaction was allowed to stir for onehour at room temperature at which time it was diluted with DCM andwashed with a solution of 0.5 molar HCl, dried (MgSO₄) and the solventremoved in vacuo to afford pure 145 [100%]; HPLC Method A, Rt=7.63 mins;[M+H⁺]=850.66.

27-e. Formation of an Axial Azido Derivative

To a solution of triflate 145 [1 mmol] in DMF was added NaN_(3 [)3 mmol]and the resulting reaction mixture was allowed to stir at roomtemperature for 10 hrs. The reaction mixture was concentrated in vacuo,and the residue washed with water followed by petroleum ether. The solidwas then dried to provide the product 146 [99%]; HPLC Method A, Rt=7.23mins; [M+H⁺]=743.5.

27-f. Removal of a Benzoyl Group by Transesterification

Compound 147 was prepared according to the procedure described inGeneral Method 2 and purified by column chromatography [30% ethylacetate/petroleum ethers] to afford a white solid [83%]; HPLC Method A,RT=6.53 min; [M+H]⁺=639.2.

27-g. Deprotection of the 2-Amino Group

To a solution of the sugar 147 [4.29 mmol] in DMF/MeOH [1:2, 45 mL] atroom temperature was added hydrazine hydrate [0.52 mL]. The reactionmixture was stirred for two hours at which time it was filtered and thefiltered solid washed with methanol. The filtrates were combined, thesolvents removed in vacuo, residue taken up in CHCl₃, washed withsaturated brine, dried (MgSO₄), and the solvent again removed in vacuoto provide a white solid 148 [88%]; HPLC Method A, Rt=5.96 mins;[M+H]⁺=473.3.

27-h. Reprotection of the 2-Amino Group

To a solution of the sugar 148 [0.22 mmol] in MeOH [1.25 mL] was addedphthalic anhydride [0.4 mmol] and triethylamine [1 drop] and thesolution was allowed to stir overnight. The reaction mixture was thenconcentrated in vacuo. The residue was the dissolved in dry pyridine[0.25 mL], cooled to 0° C., and acetic anhydride [60 μL] added dropwise.The reaction was allowed to stir overnight. The reaction was thenconcentrated, the residue taken up in CHCl₃ and washed with 10% citricacid solution, saturated sodium bicarbonate solution, saturated brinesolution, dried (MgSO₄), the solvent removed in vacuo, and the residuepurified by column chromatography [20% ethyl acetate/petroleum ethers]to afford the product as a white solid 149 [64%]; HPLC Method A, Rt=7.29mins; [M+H]⁺=645.35.

27-i. Glycosylation to Form the O-Methyl Glycoside

To a solution of the sugar 149 [0.775 mmol] in DCM [5 mL] was added 3angstrom molecular sieves, MeOH [12 mmol] and finally DMTST [2.32 mmol].The reaction mixture was allowed to stir for 30 mins at which time thereaction was quenched with triethylamine [2.37 mmol], filtered and thefiltrate concentrated in vacuo. The residue was taken up in DCM andwashed with water, 10% citric acid solution, saturated sodium hydrogencarbonate solution, saturated brine, dried (MgSO₄) and the solventremoved in vacuo to provide a yellow oil. The oil was purified by columnchromatography [20% ethyl acetate/petroleum ethers] to provide theproduct as a yellow oil [79%]; HPLC Method A, Rt=7.20 mins;[M+Na]⁺=651.3.

27-j. Zemplen Deprotection

Compound 150 was prepared according to the procedure described inGeneral Method 2 and was purified by column chromatography [25% ethylacetate/petroleum ethers] as a white solid [67%]; HPLC Method A, Rt=6.88mins; [M+Na]⁺=609.7.

27-k. Formation of an O-Me Glycoside, Beta 1-3 Linked Disaccharide

Donor 60 [0.128 mmol] and acceptor [85.2 mmol] were dissolved 1,2-DCE[1.0 mL]. 4 Angstrom molecular sieves were added and the mixture wasstirred for 15 mins. TMSOTf [2.8 μmol] was then added and the reactionleft to stir for 90 mins. The reaction mixture was then quenched withtriethylamine, diluted with CHCl₃, washed with saturated NaHCO₃solution, dried (MgSO₄) and the solvents removed in vacuo. The residuewas purified by column chromatography to afford 151 [20%]; HPLC MethodA, Rt=7.60 mins; [M+Na]⁺=1226.67

EXAMPLE 28 Formation of Alternatively Linked Disaccharide Scaffolds

28-a. Glycosylation with a Trichloroacetimidate Donor to AffordDisaccharides (153-a to 153-h)

To solutions of the acceptor molecules 152a-152h (1.8 mmol) and thedonor 2 (2.7 mmol) in dry 1,2-dichloroethane (84 mL) is added 3 Aacid-washed molecular pellets (4 g) and the resulting mixture stirredfor 20 min. To the mixture was then added Methyl Triflate (1.8 mL of a0.1M solution in dry 1,2-dichloroethane, 0.18 mmol) and the reactionthen stirred for 30 mins. After this time triethylamine (6 mL) was addedand the suspension filtered, washed with dichloromethane and all solventremoved in vacuo. This residue was purified by column chromatography toyield the title compounds as indicated in table 3 below.

TABLE 3 Disaccharide Products From Glycosylation with Donor 2 AcceptorProduct

28-b. Azide Reduction and deprotection (154a-154h)

Compounds 153a-153h are hydrogenolysed at 60 psi for 1 hour withcatalytic 10% palladium on activated charcoal in ethanol, to yield uponfiltration and evaporation, the corresponding diamines in which thebenzylidene ring has also been cleaved as indicated in the table below.These diamines may be used in their crude form for further reactions.

28-c. Amide Formation-HBTU Coupling (155a-155h)

Compounds 155a(i)-155a(iv) to 155h(i)-155h(iv) are prepared by reactionof the diamines 154a to 154h with carboxylic acids according to theprocedure described in General Method 4 in a combinatorial manner. Thisevery diamine may be reacted with an excess of every carboxylic acid toproduce the bis-amide products.

TABLE 4 Acids i-iv Shown Below are Reacted with Diamines to GiveProducts as Listed

Acids Diamine i ii iii iv 154a 155a(i) 155a(ii) 155a(iii) 155a(vi) 154b155b(i) 155b(ii) 155b(iii) 155b(vi)  154c1  155c1(i)  155c1(ii) 155c1(iii)  155c1(vi)  154c2  155c2(i)  155c2(ii)  155c2(iii) 155c2(vi) 154d 155d(i) 155d(ii) 155d(iii) 155d(vi) 154e 155e(i)155e(ii) 155e(iii) 155e(vi) 145f 155f(i) 155f(ii) 155f (iii) 155f(vi)154g 155g(i) 155g(ii) 155g(iii) 155g(vi) 154h 155h(i) 155h(ii) 155h(iii)155h(vi) Examples of Table 4

28-d. Silyl Deprotection

The t-butyldiphenylsilyl groups are removed from Compounds 155 (asappropriate) by treatment of the silylated compound inN,N-dimethylformamide with tetrabutylammonium fluoride, followed byremoval of the solvents in vacuo and purification by mass basedfractionation on a C18 HPLC column.

EXAMPLE 29 Formation of Alternatively Amide Linked DisaccharideScaffolds Reduction of an Azide to an Amine

Amino sugars can be obtained by reduction of corresponding azido sugarsaccording to the procedure described in General Method 3. Alternatively,the azide may be reduced selectively by hydrogenolysis at atmosphericpressure over 5% palladium on charcoal in methanol for 30 minutes. Thislatter method is suitable for the reduction of azides in the presence ofbenzyl ethers. Filtration of the solution and removal of the solvents invacuo yields the crude aminosugar suitable for further reaction.Hydrogenolysis is also employed to remove the carbobenzyloxy group fromcompound 152d (see Amines Used in Example 28).

Formation of an Anhydride and Reaction with an Amine

Anhydrides are formed according to the following general method. Azaleicacid monomethyl ester, suberic acid monomethyl ester or fumaric acidmonoethyl ester [2 equivalents] are dissolved in anhydrousdichloromethane to form a 10 milillolar solution. To this solution isadded diisopropylcarbodiimide [1 equivalent] and triethylamine [1equivalent] and the solution stirred at room temperature for 45 minutes.After this time, the solution of acid anhydride is evaporated,redissolved in N,N-dimethylformamide to form a 10 millimolar solutionand added to a solution of the crude sugar amine (selected from AminesUsed in Example 28) in N,N-dimethylformamide. The reaction mixture isstirred for 1 hour. The reaction mixture is quenched with water,acidified to pH 4 and extracted with ethyl acetate and back extractedwith 10% sodium hydrogen carbonate solution to yield the crude sugaramide. The solvents are removed in vacuo and the esters hydrolysed bythe addition of 5 equivalent of lithium hydroxide to an wet methanolicsolution of the crude ester. Acidification of this mixture followed byremoval of the solvents in vacuo yields the crude half acid amide whichis partially purified by passing through a short bed of silica gel. Thiscrude material in which all other protecting esters have been cleaved issuitable for further reaction. Compounds formed by this process aredisplayed in Half Acid Amides formed in Example 29 below.

Formation of a Dimeric Derivative

The crude sugar half acid amide, is then dissolved inN,N-dimethylformamide and treated with 1 equivalent of ethyldiisopropylamine, 1 equivalent of HBTU and finally 1.3 equivalents ofthe crude sugar amine. The reaction mixture is stirred for 30 to 60minutes at room temperature, quenched by the addition of water andsolvents removed in vacuo The crude residue is finally purified by massbased fractionation to furnish the desired bis amide linked scaffolds. Acombinatoral matrix of acid and amine results in a wide diversity of bisamide linked scaffolds as exemplified in Table 5.

Amines used in Example 29:

Half Acid Amides formed in Example 29:

TABLE 5 Products Resulting From Reaction of Compounds From “Amines usedin Example 29”, with “Half Acid Amides formed in Example 29” Amine Acid13 156 50 59 152d 157A 157A13 157B 157B13 157C 157C13 158A 158A13158A156 158B 158B13 158B156 158C 158C13 158C156 159A 159A13 159A156159A50 159B 159B13 159B156 159B50 159C 159C13 159C156 159C50 160A 160A13160A156 160A50 160A59 160B 160B13 160B156 160B50 160B59 160C 160C13160C156 160C50 160C59 161A 161A13 161A156 161A50 161A59 161A152d 161B161B13 161B156 161B50 161B59 161B152d 161C 161C13 161C156 161C50 161C59161C152d Example structures from Table 5:

EXAMPLE 30 Formation of Amide Linked Disaccharide Scaffolds

Glucuronic acid 14, is dissolved in N,N-dimethylformamide to form a 10millimolar solution. To this solution is added triethylamine [1.1equivalents] followed by HBTU [1.05 equivalents. The mixture is stirredfor 3 minutes at room temperature, after which time a concentratedsolution of the amine [20-30 millimolar; 1 equivalent], as prepared inExample 29 [amines 13, 156, 152d, 50 and 59] is rapidly added. Thereaction mixture is stirred for a further 45 minutes, then quenched withan equal volume of 10% citric acid in water, and extracted with ethylacetate. The organic layers are dried over magnesium sulfate andsolvents removed in vacuo to yield the crude product which is furtherpurified by column chromatography, to yield the desired product.

Reaction Products:

The Boc, isopropylidene and benzylidene protecting groups may be removedby treatment with TFA according to general procedure 5, acetate andbenzoate protecting groups are removed according to general procedure 2.

EXAMPLE 31 Synthesis of an Alkylated 2-Deoxy-2-Amino DisaccharidicCompound

31-a and 31-b. N-Alkylation

(31-a). To a solution of the sugar 109-03 [7.4 mg] in THF/MeOH [84μL/9.4 μL] was added benzaldehyde [0.71 μL] and the mixture stirred for2 hrs at room temperature. To the mixture was then added acetic acid[0.5 μL] and NaCNBH₃ [0.8 mg] and the reaction was allowed to stirovernight at room temperature. The reaction was neutralised andconcentrated in vacuo. The residue was taken up in DCM and washed with asaturated brine solution, dried (MgSO₄) and the solvent removed invacuo. (31-b). The residue was treated with Ac₂O/pyridine [1:3] solutionfor two hours for the purpose of analysis; HPLC Method A, Rt (168monobenzylated-monoacetylated)=7.56 mins, (169 bis-benzylated)=8.77mins; mono-benzylated-mono-acetylated [M+H]⁺=1391.9, bis-benzylated[M+H]⁺=1339.9.

EXAMPLE 32 Synthesis of Benzimidazole Compounds

32-a. Fluorine Displacement

A solution of 3-fluoro-2-nitro-trifluoromethylbenzene [0.0715 mmol],triethylamine [0.0861 mmol] in DMF [250 μL] was added to a flaskcontaining diamine 68 [0.0241 mmol]. The resulting reaction mixture wasthen stirred at 50° C. for 16 hrs. At this time the reaction was allowedto cool and the product was purified by preparative TLC [mobile phaseethyl acetate]. The product was collected in quantitative yield; HPLCMethod A, Rt=7.51 mins; [M+Na]⁺=1230.6

32-b. Formation of Benzimidazole

A solution of SnCl_(2 [)300 μL of SnCl₂.H₂O at 0.32 molar in DMF] wasadded to a flask containing compound 170 [2.48 μmol]. The reactionmixture was then stirred at 80° C. for 16 hrs. The reaction mixture wasdiluted with EtOAc/H₂O [1:1, 5 mL], filtered through a pad of celite.The filtrated was separated into aqueous and organic layers and theorganic layer washed with H₂O, dried (MgSO₄) and the solvent removed invacuo to afford a mixture of products 171 and 172; HPLC Method A, Rt(171)=7.18 mins, Rt (172)=7.41 mins; [M+H]⁺ (171)=1186.8, [M+H]⁺(172)=11.58.8.

EXAMPLE 33 Synthesis of a N-Acetyl-lactosamine Based Library of6′-Hydroxy Phosphonates

Reactions were carried out in identical series for resins 174-1 andseries 174-2. After step 33). After step 33-b each series was dividedinto 12 portions for the individual alkylations.

Alkylating Agents for Example 33, where R=Sulphonate or R=Halide.

33-a. Glycosylation

Resin [0.47 mmol] was weighed into a reactor and molecular sieves [200mg], thioglycoside donor sugar 174 [2.35 mmol] and dichloromethane [˜1.5mL] was added. To the mixture was then added DMTST [2.35 mmol]. Thereaction vessel was sealed, shaken and reacted for 5 hours. At this timethe reaction was then quenched by the addition of triethylamine, and themolecular sieves removed from the resin. The resin was then washed withDMF, MeOH/CHCl₃ (1:1) and dichloromethane. The resin was then driedunder vacuum.

33-b. Solid Phase Silylether Deprotection

A solution of PSHF (proton sponge hydrogen fluoride) (0.5 Molar inDMF/Acetic Acid, 95:5) was prepared. The resins [1.41 mmol] was added tothe solution and the reaction was stirred at 65° C. for 24 hours. Therein was then washed with DMF, MeOH/CH₃COOH/THF, 1:1:8, THF and DCM, andthen dried under high vacuum.

33-c. Solid Phase Alkylation

Resins 176 [0.047 mmol] were individually reacted with a 0.25 molarsolution of tert-butoxide in DMF (5 min) and then an alkylating agent(see above), [0.25 molar of alkylating agent in DMF, 20 min] was reactedwith the resin. The resins were washed with DMF and again treated withthe two solutions, this procedure was repeated a further four times. Thefinal wash of the resins was performed as above; with DMF,THF/MeOH/CH₃CO₂H (8:1:1), THF, DCM and MeOH. The resins were then driedovernight.

33-d. Cleavage of Disaccharide from Resin

The resins 177 [0.047 mmol] were separately treated with a 7% hydrazinehydrate/DMF solution [2 mL] overnight. The resin was filtered and theresin washed with DMF. The filtrates were combined and the solventremoved in vacuo. The residue was taken up in DCM and washed with waterand saturated brine solution, dried (MgSO₄) and the solvent removed invacuo. The residue was then treated with a solution of Ac₂O/pyridine [1mL, 1:3] for three hours. The Solvents were removed in vacuo and theproduct purified by column chromatography.

33-e. Removal of the Pivaloyl Protecting Group

To a solution of NaOMe/MeOH/THF [2 mL, ˜2 molar] was added the pivaloylprotected disaccharide 178 [0.03 mmol]. The reaction mixture was heatedat reflux until TLC indicated the reaction was complete. At completion,reaction mixture pH was reduced to ˜5 with amberlite IR-120-H⁺ resin.The reaction was filtered, and the solvent concentrated in vacuo

33-f. Deprotection of Hydroxyphosphonates and Benzyl Ether Cleavage

Compound 178 (after 33-e) [0.0193 mmol] was dissolved in drydichloromethane [2 mL] under a nitrogen atmosphere, the solution cooledto 0° C. and trimethylsilyl bromide [0.097 mmol] was added. Afterstirring at 0° C. for 30 mins a solution of ammonia in methanol [12 μLof 28% aq ammonia in 20 mL methanol] was added. The solvents wereremoved to give the crude free hydroxyphosphonate as an ammonium salt.Final products were purified by mass fractioning HPLC.

TABLE 6 Final products Synthesised in Example 33.

Comp. No. R R1 R2 Note 179a Ra H OMe 179b Rb H OMe 179c Rc H OMe 179d RdH OMe 179e Re H OMe 179f Rf H OMe 179g Rg H OMe 179h Rh H OMe 179i Ri HOMe 179j Rj H OMe 179k Rk H OMe 179l Rl H OMe 179m Ra H,OH OH,H Anomericlactol 179n Rb H,OH OH,H Anomeric lactol 179o Rc H,OH OH,H Anomericlactol 179p Rd H,OH OH,H Anomeric lactol 179q Re H,OH OH,H Anomericlactol 179r Rf H,OH OH,H Anomeric lactol 179s Rg H,OH OH,H Anomericlactol 179t Rh H,OH OH,H Anomeric lactol 179u Ri H,OH OH,H Anomericlactol 179v Rj H,OH OH,H Anomeric lactol 179w Rk H,OH OH,H Anomericlactol 179x Rl H,OH OH,H Anomeric lactol Side Arms for Table 6

EXAMPLE 34 Preparation of Guanidine

34-a. Reaction Conditions to form a Thiourea

Compounds 111-14 and 180 were prepared as a mixture (unpurified) byreaction of compound 110-20 according to the procedure described inGeneral Method 12. The mixture was used directly in the next step.

34-b. Formation of a Guanidine

The sugar mixture (111-14 and 180) (0.025 mmol) was dissolved inmethanol (0.5 mL) and concentrated aqueous ammonium hydroxide (0.5 ml)was added. The reaction was stirred at room temperature for 4 hours. Thesolvents were then removed in vacuo and the residue purified by LCMS.

In a cognate manner, benzylamine, ethylamine, and other primary orsecondary amines can be substituted for ammonia to yield thecorresponding substituted guanidiniums. Products are shown in table 7.

TABLE 7 Guanidinium products

Prod- Starting Synth. Rt Yield uct material method R5* R2 R3 R4 M + H(mins) (%) 180 110-20 12 H C A I 937.5  6.31 49 181 111-31 17 H C A I800.37 5.23 75 182 110-20 34-b Bn C A I ND ND ND 183 110-20 34-b Et C AI ND ND ND 184 110-20 34-b Me C A I ND ND ND R5* substituents areHydrogen (H), Benzyl (Bn), Ethyl (Et), or Methyl (Me): SubstituentsR2-R4 are as found in Table 2, Example 24.

-   I. K. C. Nicolaou; J. M. Salvino, K. Raynor; S. Pietranico; T.    Reisine; R. M. Freidinger, R. Hirschmann, Pept.: Chem., Struct.    Biol., Proc. Am. Pept. Symp., 11^(th), 1990-   II. (a) H. Kunz, T. Wundberg, C. Kallus, T. Opatz, S. Henke, W.    Schmidt, Angew. Chem. Int. Ed., 1998, 37, No. 18, (b) K. Kallus, T.    Wundberg, W. Schmidt, S. Henke, H. Kunz, Tet. Lett., 40, 1999,    7783-7786, (c) U. Hünger, T. Maidhof, O. Knöll, H. Kunz, Poster    Presentation, 20^(th) International Carbohydrate Symposium,    Hamburg-Germany, (d) T. Opatz, C. Kallus, T. Wundberg, W.    Schmidt, S. Henke, H. Kunz, Poster Presentation, 20^(th)    International Carbohydrate Symposium, Hamburg-Germany.-   III. R. Hirschmann, K. C. Nicolaou, S. Pietramico, J. Salvino, E. M.    Lealy, W. C. Shakepeare, P. S. Spengler, P. Hamley, A. B. Smith, T.    Reisine, K. Raynor, C. Donaldson, W. Vale, L. Maechler, R. M.    Freidinger, C. D. Strader, J. Am. Chem. Soc., 1993, 115, 12550

1. A disaccharide compound of formula IA-d-L-e-B  formula I wherein A and B are independently chosen from

T is O or CH₂; R6 and R7 are hydrogen, or together form a carbonyloxygen; R1 is hydrogen, —N(Z)Y, C(Z)Y, OZ or SZ wherein; when R1 isN(Z)Y Y is selected from the group consisting of hydrogen or thefollowing;

wherein; Z is selected from hydrogen or X1, Q is selected from hydrogenor W, W is selected from the group consisting of alkyl, alkenyl,alkynyl, heteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of1 to 20 atoms, X1 is selected from the group consisting of alkyl,alkenyl, alkynyl, heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl,heteroaryl, arylalkyl or heteroarylalkyl of 1 to 20 atoms, where R1 isC(Z)Y; Y, is absent or is selected from hydrogen, double bond oxygen(═O) to form a carbonyl, or triple bond nitrogen to form a nitrile, Z isabsent or is selected from hydrogen or X2, wherein X2 is selected fromthe group consisting of alkyl, alkenyl, alkynyl, heteroalkyl,aminoalkyl, aminoaryl, aryloxy, alkoxy, heteroaryloxy, aminoaryl,aminoheteroaryl, thioalkyl, thioaryl or thioheteroaryl, acyl, arylacyl,heteroarylacyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of 1 to20 atoms, where R1 is OZ or SZ, Z is selected from hydrogen or X3,wherein X3 is selected from the group consisting of alkyl, alkenyl,alkynyl, heteroalkyl, acyl, arylacyl, heteroarylacyl, aryl, heteroaryl,arylalkyl or heteroarylalkyl of 1 to 20 atoms, The groups R2, R3, R4 andR5 are selected from the group consisting of hydrogen, N₃, OH, OX4,N(Z)Y, wherein N(Z)Y is as defined above or Y is

where Q and W are as defined above, and X4 is independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, heteroalkyl,aminoalkyl, aminoaryl, aryloxy, alkoxy, heteroaryloxy, aminoaryl,aminoheteroaryl, alkylcarbamoyl, arylcarbamoyl or heteroarylcarbamoyl,acyl, arylacyl, heteroarylacyl, aryl, heteroaryl, arylalkyl orheteroarylalkyl of 1 to 20 atoms, d and e represent the connectionpoints for A and B and replace one of the groups R1, R2, R3, R4, or R5in each of the groups A and B and form the connection point for thelinker L, d and e form a covalent bond or are selected from the groupconsisting of:

L is absent, or is selected from the group consisting of alkyl,cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heteroalkyl,cycloheteroalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl of 1 to12 atoms.
 2. The compound of claim 1, wherein when R1 is N(Z)Y, W issubstituted with at least one moiety selected from the group consistingof OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy,aryloxy, amidine, guanidiniums, carboxylic acid, carboxylic acid ester,carboxylic acid amide, aryl, cycloalkyl, heteroalkyl, heteroaryl,aminoalkyl, aminodialkyl, aminotrialkyl, aminoacyl, carbonyl,substituted or unsubstituted imine, sulfate, sulfonamide, phosphate,phosphoramide, hydrazide, hydroxamate, and hydroxamic acid.
 3. Thecompound of claim 1, wherein when R1 is N(Z)Y, Z and Y are combined toform a monocyclic or bicyclic ring structure of 4 to 10 atoms.
 4. Thecompound of claim 1, wherein X1 is substituted with at least one moietyselected from the group consisting of OH, NO, NO₂, NH₂, N₃, halogen,CF₃, CHF₂, CH₂F, nitrile, alkoxy, aryloxy, amidine, guanidiniums,carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl,cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl,aminotrialkyl, aminoacyl, carbonyl, substituted or unsubstituted imine,sulfate, sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate,and hydroxamic acid.
 5. The compound of claim 1, wherein; when R1 isC(Z)Y; X2 is substituted with at least one moiety selected from thegroup consisting of OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂, CH₂F,nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid,carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl,heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminotrialkyl,aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate,sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate,hydroxamic acid, heteroaryloxy, aminoalkyl, aminoaryl, aminoheteroaryl,thioalkyl, thioaryl and thioheteroaryl.
 6. The compound of claim 1,wherein; when R1 is C(Z)Y; Z and Y form a ring structure of 4 to 10atoms.
 7. The compound of claim 6, wherein the ring structure issubstituted by X1 groups.
 8. The compound of claim 1, wherein; when R1is OZ or SZ; X3 is substituted with at least one moiety selected fromthe group consisting of OH, NO, NO₂, NH₂, N₃, halogen, CF₃, CHF₂, CH₂F,nitrile, alkoxy, aryloxy, amidine, guanidiniums, carboxylic acid,carboxylic acid ester, carboxylic acid amide, aryl, cycloalkyl,heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl, aminodialkyl,aminoacyl, carbonyl, substituted or unsubstituted imine, sulfate,sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate,hydroxamic acid, heteroaryloxy, aminoalkyl, aminoaryl, aminoheteroaryl,thioalkyl, thioaryl and thioheteroaryl.
 9. The compound of claim 1,wherein; when R1 is OZ or SZ; X4 is substituted with at least one moietyselected from the group consisting of OH, NO, NO₂, NH₂, N₃, halogen,CF₃, CHF₂, CH₂F, nitrile, alkoxy, aryloxy, amidine, guanidiniums,carboxylic acid, carboxylic acid ester, carboxylic acid amide, aryl,cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl, aminodialkyl,aminotrialkyl, aminoacyl, carbonyl, substituted or unsubstituted imine,sulfate, sulfonamide, phosphate, phosphoramide, hydrazide, hydroxamate,and hydroxamic acid.
 10. The compound of claim 1, wherein Z and Y arecombined to form a ring structure of 4 to 10 atoms.
 11. The compound ofclaim 10, wherein the ring structure is substituted with X1 groups. 12.The compound of claim 1, wherein L is substituted with at least onemoiety selected from the group consisting of OH, NO, NO₂, NH₂, N₃,halogen, CF₃, CHF₂, CH₂F, nitrile, alkoxy, aryloxy, amidine,guanidiniums, carboxylic acid, carboxylic acid ester, carboxylic acidamide, aryl, cycloalkyl, heteroalkyl, heteroaryl, aminoalkyl,aminodialkyl, aminotrialkyl, aminoacyl, carbonyl, substituted orunsubstituted imine, sulfate, sulfonamide, phosphate, phosphoramide,hydrazide, hydroxamate, hydroxamic acid, heteroaryloxy, aminoalkyl,aminoaryl, aminoheteroaryl, thioalkyl, thioaryl and thioheteroaryl. 13.The compound of claim 1, wherein in group A, T is oxygen, group A is apyranose ring, and the linker, d-L-e, is a glycosidic linkage formedbetween the anomeric position R1 of group A, and any position R1 to R5of group B, such that the d is (—O—), L is absent, and e is a covalentbond.
 14. The compound of claim 13, wherein the structure of formula 1is


15. The compound of claim 13, wherein the structure of formula 1 is


16. The compound of claim 13, wherein the structure of formula 1 is


17. The compound of claim 13, wherein the structure of formula 1 is


18. The compound of claim 13, wherein the structure of formula 1 is


19. The compound of claim 13, wherein the structure of formula 1 is


20. The compound of claim 13, wherein the structure of formula 1 is


21. The compound of claim 13, wherein the structure of formula 1 is


22. The compound of claim 13, wherein the structure of formula 1 is


23. The compound of claim 1, wherein in group A, T is oxygen, group A isa pyranose ring, the linker, d-L-e, forms an amide linkage in which R6and R7 of A is a C═O, R5 is d which is a covalent bond, L is absent, andany of R1, R2, R3, R4, R5 on B is e which is


24. The compound of claim 23, wherein the structure of formula 1 is


25. The compound of claim 23, wherein the structure of formula 1 is


26. The compound of claim 23, wherein the structure of formula 1 is


27. The compound of claim 23, wherein the structure of formula 1 is


28. The compound of claim 23, wherein the structure of formula 1 is


29. The compound of claim 23, wherein the structure of formula 1 is


30. The compound of claim 23, wherein the structure of formula 1 is


31. The compound of claim 23, wherein the structure of formula 1 is


32. The compound of claim 23, wherein the structure of formula 1 is


33. The compound of claim 1, wherein in group A, T is oxygen, bothgroups A and B are pyranose rings, the linkage, d-L-e, is an ether typelinkage in which any of R1 to R5 in group A and group B is d and erespectively and is

and L is present.
 34. The compound of claim 33, wherein the structure offormula 1 is


35. The compound of claim 33, wherein the structure of formula 1 is


36. The compound of claim 33, wherein the structure of formula 1 is


37. The compound of claim 33, wherein the structure of formula 1 is


38. The compound of claim 33, wherein the structure of formula 1 is


39. The compound of claim 33, wherein the structure of formula 1 is


40. The compound of claim 33, wherein the structure of formula 1 is


41. The compound of claim 33, wherein the structure of formula 1 is


42. The compound of claim 33, wherein the structure of formula 1 is


43. The compound of claim 33, wherein the structure of formula 1 is


44. The compound of claim 33, wherein the structure of formula 1 is


45. The compound of claim 33, wherein the structure of formula 1 is


46. The compound of claim 33, wherein the structure of formula 1 is


47. The compound of claim 33, wherein the structure of formula 1 is


48. The compound of claim 33, wherein the structure of formula 1 is


49. The compound of claim 33, wherein the structure of formula 1 is


50. The compound of claim 33, wherein the structure of formula 1 is


51. The compound of claim 33, wherein the structure of formula 1 is


52. The compound of claim 33, wherein the structure of formula 1 is


53. The compound of claim 33, wherein the structure of formula 1 is


54. The compound of claim 33, wherein the structure of formula 1 is


55. The compound of claim 33, wherein the structure of formula 1 is


56. The compound of claim 33, wherein the structure of formula 1 is


57. The compound of claim 33, wherein the structure of formula 1 is


58. The compound of claim 33, wherein the structure of formula 1 is


59. The compound of claim 1, wherein in group A, T is oxygen, thelinkage, d-L-e, is a linkage in which R1 in group A is d, is selectedfrom the group consisting of a covalent bond,

L is present; and e is selected from the group consisting of

and the connection to the B ring is at any of R1-R5.
 60. The compound ofclaim 59, wherein the structure of formula 1 is


61. The compound of claim 59, wherein the structure of formula 1 is


62. The compound of claim 59, wherein the structure of formula 1 is


63. The compound of claim 59, wherein the structure of formula 1 is


64. The compound of claim 1, wherein in group A, T is oxygen, thelinkage, d-L-e, is a linkage in which R1 in group A is d, R1 in group Bis e, and both d and e are independently chosen from the groupconsisting of: a covalent bond;

and L is present.
 65. The compound of claim 64, wherein the structure offormula 1 is


66. The compound of claim 64, wherein the structure of formula 1 is


67. The compound of claim 1, wherein in group A, T is oxygen, thelinker, d-L-e, is a linkage in which at least one R group R1 to R5 ingroup A is d and is selected from the group consisting of

and any one of R1 to R5 in group B is e and e is

L is present.
 68. The compound of claim 67, wherein the structure offormula 1 is


69. The compound of claim 67, wherein the structure of formula 1 is


70. The compound of claim 67, wherein the structure of formula 1 is


71. The compound of claim 67, wherein the structure of formula 1 is


72. The compound of claim 1, wherein in group A, T is oxygen, thelinkage, d-L-e, is a linkage in which at least one R group R1 to R5 ingroups A and B is d and e and d and e are independently selected fromthe group consisting of

and L is present.
 73. The compound of claim 72, wherein the structure offormula 1 is


74. The compound of claim 72, wherein the structure of formula 1 is


75. The compound of claim 72, wherein the structure of formula 1 is


76. The compound of claim 72, wherein the structure of formula 1 is


77. The compound of claim 72, wherein the structure of formula 1 is


78. A method of synthesizing a disaccharide compound of claim 1comprising reacting compound A and compound B in solution.
 79. A methodof combinatorial synthesis of compounds of claim 1 comprising the stepof immobilizing a compound of group B onto a support through at leastone of the functionalized positions R1 to R5.
 80. The method of claim79, wherein the support is selected from the group consisting ofderivatised polystyrene, tentagel, wang resin, MBHA resin,aminomethylpolystyrene, rink amide resin DOX-mpeg, and polyethyleneglycol.
 81. A method of synthesising a compound of formula I insolution, comprising the step of reacting compound A with a linker groupL to form a compound A-d-L and further reacting the compound A-d-L withcompound B to form a compound of formula I.
 82. A method of synthesisinga compound of formula I in solution, comprising the step of reactingcompound B with a linker group L to form a compound B-e-L and furtherreacting the compound B-e-L with compound A to form a compound offormula I.